ADIPONECTIN LEVELS IN GRAVES' DISEASE - SYSTEMATIC REVIEW AND META-ANALYSIS.

Context: Graves' disease is the most prevalent cause of hyperthyroidism worldwide. Adiponectin, the most abundant adipokine, plays a significant role in a cluster of prevalent diseases connected to metabolic disorders. Objective: Although the association between adiponectin and Graves' disease has been studied, the existing data is inconsistent. Therefore, we conducted this systematic review and meta-analysis to evaluate the relationship between adiponectin levels and Graves' disease. Methods: We performed a systematic electronic search on PubMed, EMBASE, Scopus and Cochrane Library using predefined keywords. We used the NHLBI quality assessment tools to assess the included studies. Results: There were 11 studies involving 781 subjects included in our qualitative synthesis, while 6 studies were included in our quantitative synthesis. We observed significantly increased adiponectin levels in Graves' disease patients compared to controls (MD 2.983 [95% CI 0.138-5.828]) and hypothyroidism patients (MD 3.389 [95% CI 1.332-5.446]). Nevertheless, no significant MD was observed when comparing Graves' disease patients with and without Graves' ophthalmopathy (MD -27.124 [95% CI -88.893 - 34.645]). Conclusions: Adiponectin levels were significantly higher in patients with Graves' disease compared to controls and hypothyroidism patients. However, patients with and without Graves' ophthalmopathy did not present a significant mean difference in adiponectin levels.

Translation, cultural adaptation and validation of the revised patients' attitudes towards deprescribing (rPATD) questionnaire in Romanian older adults.

BACKGROUND: Deprescribing is part of ensuring appropriate medication use and may reduce medication-related harm. Capturing the beliefs and attitudes of patients towards deprescribing by using a validated tool may support optimizing medication use in practice. OBJECTIVES: To translate, culturally adapt and validate the revised Patients' Attitudes Towards Deprescribing (rPATD) questionnaire in Romanian and to investigate the attitudes and beliefs of older adults towards deprescribing. METHODS: The rPATD questionnaire was translated using forward-backward translation into Romanian and culturally adapted. The psychometric properties were evaluated in older adults ≥65 years of age. Structural validity was assessed by item load on factors using an exploratory factor analysis (EFA) which was compared to the original English version and the internal consistency by Cronbach's alpha. Construct validity was evaluated by calculating the Spearman's rank correlation coefficients between the factor scores obtained using the revised version of the Romanian rPATD and scores on the Beliefs about Medicines Questionnaire (BMQ) Specific Concerns Romanian version. Floor and ceiling effect were also examined. RESULTS: We translated the questionnaire and administered it to 224 participants (median age 72 years [interquartile range: 68.0; 77.0]). In the EFA individual items loaded onto 4 factors, grouped similarly to the English version (Involvement, Burden, Appropriateness, Concerns about Stopping factors). Two items from each of the Involvement and Appropriateness factors were removed to improve factor loading and avoid cross-loading. The Cronbach's alpha values for the 4 factors ranged between 0.522 and 0.773. The scores for Burden and Concerns about Stopping factors were found to be positively correlated with BMQ Specific Concerns score. We identified a ceiling effect for one of the four factors (Involvement) and no floor effects. CONCLUSIONS: The Romanian rPATD was validated in 4 factor structure similar to the original English questionnaire. The Romanian version of the questionnaire may support the health care professionals in Romania to initiate and support patient-centered deprescribing.

Leptin involvement in the survival of pancreatic adenocarcinoma patients with obesity and diabetes.

OBJECTIVE: Current molecular characterization of pancreatic ductal adenocarcinoma (PDAC) does not incorporate the host reaction to cancer cells and cannot predict the response to chemo- or immunotherapy. Leptin is an adipokine involved in regulating energy balance with a possible role in the development of obesity-associated cancers, but its relationship with other pathways in pancreatic carcinogenesis has not been established yet. The aim of this prospective study was to assess the involvement of leptin and phosphoinositide 3-kinase (PI3K) in the survival of overweight and/or diabetic patients with PDAC. PATIENTS AND METHODS: A total of 112 patients were included, 56 diagnosed with PDAC and 56 age and sex-matched healthy controls, with a maximum follow-up of 24-months. The circulating leptin, interleukin 1-beta, tumor factor necrosis-alpha, and PI3K were measured by enzyme-linked immunosorbent assay (ELISA). A multivariate Cox regression model was used to determine the factors influencing survival. RESULTS: The serum levels of leptin [38.5 (31.6-47.0) pg/ml] and other cytokines in PDAC patients were similar to controls, irrespective of the presence of diabetes. No significant correlation between the biomarkers was found. In obese and overweight patients, the leptin level and survival rate were lower than in non-obese patients. CONCLUSIONS: The leptin level was not associated with the presence of PDAC, although it was lower in obese and overweight patients who had lower survival. No association with inflammatory biomarkers or PI3K was noted. Furthermore, leptin levels had no independent role in survival, suggesting that the prognostic role of obesity in PDAC is based on a different pathway.

Reconstruction of the pelvic ring in iliac or iliosacral resections: allograft or autograft?

BACKGROUND: The necessity to reconstruct the pelvic ring after an iliac or iliosacral resection is still debated. Different reconstructive techniques are available, including autologous and homologous graft and custom-made prosthesis. The aim of this study was to evaluate the functional outcome and complications of patients who underwent resection of iliac bone and part of the sacrum for primary bone tumour and reconstruction with an allograft or autograft. METHODS: We retrospectively evaluated 18 patients (10 males and 8 female) with a mean age of 28 years (range 9-56) who were operated between 1992 and 2015. Six patients were reconstructed with an autograft (Group A) and 12 patients with an allograft (Group B). All complications were recorded. At final follow-up, patients with the original reconstruction still in site were functionally evaluated with MSTS Score. RESULTS: Mean follow-up time was 107 months (range 4-221). Two patients (11.1%) had an external hemipelvectomy for local recurrence, and 3 patients died of the disease. Mean MSTS Score was comparable between the two groups 21.7 (range 20-25) in Group A and 19.9 (range 4-28) in Group B. Patients with partial sacral resection had an increased risk of local recurrence and lower MSTS Score [15.5 (range 7-20) vs. 22.2 (range 4-28)]. CONCLUSIONS: Biological reconstruction of pelvic ring with autologous or homologous bone graft gives acceptable functional results. However, the decision on how to reconstruct the pelvic ring after iliac resection should be taken on a patient-by-patient basis.

Quality of Life in Patients with Acromegaly - A Romanian Single Center Cross-Sectional Study.

CONTEXT: Acromegaly, a severe condition characterized by excessive and unmodulated secretion of growth hormone, leads to morphologic disturbances and multisystem complications. OBJECTIVE: The purpose of this study was to evaluate the quality of life (QOL) in patients with acromegaly compared to matched obese patients. DESIGN: This was an observational cross-sectional study. SUBJECTS AND METHODS: We enrolled 49 patients with acromegaly and 49 obese patients. AcroQoL (acromegaly QoL questionnaire) was applied to all patients and IGF-1 (type 1 insulin-like growth factor 1) was measured. RESULTS: Patients with acromegaly had a worse QoL compared to patients with obesity (score= 77(53-86) vs. 96(90-102), p<0.001). In the group of patients with acromegaly, there was no difference in the QoL regarding the activity of the disease (active, controlled, or cured). Men had a higher AcroQoL score than women (score= 88(55-95) vs. 74(52.75-82), p=0.02), but there was no difference between patients with microadenomas and the ones with macroadenomas (score= 82(66-88.5) vs. 73(55-83), p=0.136). The most frequent complications were cardiovascular complications (81.63%), articular complications (73.46%), dyslipidemia (65.30%) and digestive complications (63.26%). CONCLUSIONS: Despite complex treatment and hormonal control, the presence of complications reduces the quality of life in patients with acromegaly, even when compared with obese patients.

Programmed cell death protein-1 (PD-1)/programmed death-ligand-1 (PD-L1) axis in hepatocellular carcinoma: prognostic and therapeutic perspectives.

Hepatocellular carcinoma (HCC) is the most common primary neoplasia of the liver. There have been tremendous efforts in the development of therapeutic strategies in the last decades. As opposed to other cancer entities immunotherapy has just recently gained popularity in HCC. Among various immunotherapy approaches, programmed cell death protein-1 (PD-1), and its ligand programmed death receptor ligand-1 (PD-L1) axis became one of the most promising pathway of the decade. The scientific interest in PD-1/PD-L1 axis is definitely justified due to: ability to detect PD-L1 expression in patients that underwent resection for HCC with prognostic values; the role of serum PD-L1 as a tool to identify early recurrences and to monitor treatment outcome; PD-1/PDL1 is a highly targetable pathway, with possible predictive markers, and with high clinical applicability that might help us in selecting a subgroup of HCC patients who are most likely to benefit from PD-1/PD-L1 inhibitors. In this review we will first discuss the prognostic role of PD-1/PD-L1 as a bio-marker in various clinical scenarios. Afterwards we will critically analyse the recently published trials with PD-1/PD-L1 inhibitors in HCC either alone or in combination with other treatment modalities. The higher focus will be on clinical rather than preclinical studies. Nevertheless, the strengths and limits of PD-1/PD-L1 axis in both prognosis and therapy of HCC will be highlighted.

An insight into statin use and its association with muscular side effects in clinical practice.

BACKGROUND: Muscular complaints are known side-effects of statin therapy, ranging from myalgia to clinically important myositis and rhabdomyolysis. We investigated the statin use and association with the presence and characteristics of muscular complaints. METHODS: We conducted a prospective observational study in internal medicine departments. Patients with statin therapy before hospitalization were interviewed for muscular complaints. When muscular complaints were reported, information on type and severity of muscular symptoms, location and time to onset was collected. RESULTS: We identified 85 patients with statin treatment at hospital admission out of 521 included. Nine (10.59%) patients reported muscular complaints associated with statin therapy. A cluster of symptoms (cramps, stiffness, decreased muscle power) was reported, affecting both upper and lower limbs. The severity of pain was in most of the cases moderate or severe. All patients reported that pain was intermittent. Five reported that pain was generalized. Symptoms appeared in the first month of treatment or three months after the drug initiation. Creatine kinase was raised in one patient. In two cases drug interactions were probably responsible for muscular complaints. CONCLUSION: In the studied set of patients muscular symptoms were a rather frequent effect of statin therapy. As this side-effect could be troublesome for patients and could lead to more severe outcomes, their timely detection and management is important.

Drug-drug Interactions of Statins Potentially Leading to Muscle-Related Side Effects in Hospitalized Patients.

INTRODUCTION: The associations of drugs that may interact with the statins resulting in elevated serum concentration of the statins are an important risk factor for statin induced muscle disorders. We aimed to determine the prevalence of these associations in all hospitalized patients that had been prescribed statins before/during hospitalization and to find out how often they are associated with muscle-related side effects. METHODS: This prospective, non-interventional study performed in two internal medicine departments included patients with statin therapy before/during hospitalization. Data on each patient demographic characteristics, co-morbidities and treatment was collected from medical charts and interviews. We evaluated patients' therapy for the targeted associations using Thomson Micromedex Drug Interactions checker and we ranked the identified drug-drug interactions (DDIs) accordingly. Each patient with statin treatment before admission was additionally interviewed in order to identify muscular symptoms. RESULTS: In 109 patients on statin treatment we found 35 potential (p) DDIs of statins in 30 (27.5%) patients, most of which were in the therapy before admission (27 pDDIs). The pDDIs were moderate (20 pDDIs) and major (15 pDDIs). Of the total number of pDDIs, 24 were targeting the muscular system. The drugs most frequently involved in the statins' pDDIs were amiodarone and fenofibrate. Two of the patients with pDDIs reported muscle pain, both having additional risk factors for statin induced muscular effects. CONCLUSION: The prevalence of statins' pDDIs was high in our study, mostly in the therapy before admission, with only a small number of pDDIs resulting in clinical outcome.