A Vicious Cycle of Osteosarcopenia in Inflammatory Bowel Diseases—Aetiology,Clinical Implications and Therapeutic Perspectives

Sarcopenia is a disorder characterized by a loss of muscle mass which leads to the reduction of muscle strength and a decrease in the quality and quantity of muscle. It was previously thought that sarcopenia was specific to ageing. However, sarcopenia may affect patients suffering from chronic diseases throughout their entire lives. A decreased mass of muscle and bone is common among patients with inflammatory bowel disease (IBD). Since sarcopenia and osteoporosis are closely linked, they should be diagnosed as mutual consequences of IBD. Additionally, multidirectional treatment of sarcopenia and osteoporosis including nutrition, physical activity, and pharmacotherapy should include both disorders, referred to as osteosarcopenia.     

Is There a FADS2-Modulated Link between Long-Chain Polyunsaturated Fatty Acids in Plasma Phospholipids and Polyphenol Intake in Adult Subjects Who Are Overweight?

Dietary polyphenols promote cardiometabolic health and are linked with long-chain polyunsaturated fatty acids in plasma phospholipids (LC-PUFA). The FADS2 polymorphisms are associated with LC-PUFA metabolism and overweight/obesity. This 4-week study examined the link between polyphenol intake, FADS2 variants (rs174593, rs174616, rs174576) and obesity in 62 overweight adults (BMI ≥ 25), allocated to consume 100 mL daily of either: Aronia juice, a rich source of polyphenols, with 1177.11 mg polyphenols (expressed as gallic acid equivalents)/100 mL (AJ, n = 22), Aronia juice with 294.28 mg polyphenols/100 mL (MJ, n = 20), or nutritionally matched polyphenol-lacking placebo as a control (PLB, n = 20). We analyzed LC-PUFA (% of total pool) by gas chromatography and FADS2 variants by real-time PCR. Four-week changes in LC-PUFA, BMI, and body weight were included in statistical models, controlling for gender and PUFA intake. Only upon AJ and MJ, the presence of FADS2 variant alleles affected changes in linoleic, arachidonic, and eicosapentaenoic acid (EPA). Upon MJ treatment, changes in EPA were inversely linked with changes in BMI (β= −0.73, p = 0.029) and weight gain (β= −2.17, p = 0.024). Only in subjects drinking AJ, the link between changes in EPA and anthropometric indices was modified by the rs174576 variant allele. Our results indicate the interaction between FADS2, fatty acid metabolism, and polyphenol intake in overweight subjects.     

Associations of Lifestyle Factors with Osteopenia and Osteoporosis in Polish Patients with Inflammatory Bowel Disease

Reduced physical activity (PA), smoking, and coffee and alcohol drinking constitute risk factors of osteoporosis in patients with inflammatory bowel disease (IBD). The aim of the study was to measure the bone mineral density (BMD) and frequency of osteopenia and osteoporosis in patients with IBD and their correlation with PA, smoking, coffee, and alcohol. The study group consisted of 208 patients with IBD-103 with Crohn’s disease (CD), 105 suffering from ulcerative colitis (UC). Densitometric measurements were performed using the DXA. All patients completed a questionnaire concerning PA, smoking, and coffee and alcohol consumption. The prevalence of osteopenia and osteoporosis (L2–L4) in the IBD group was 48.1%; in the CD group, it amounted to 48.6%, and in the UC group, the prevalence was equal to 33.3%. Patients with CD who were diagnosed with osteopenia and osteoporosis demonstrated reduced PA compared to patients with a normal BMD who exercised regularly (p = 0.0335). A similar observation was made in the group of women with IBD. Women with a normal BMD exercised significantly more often than women suffering from osteopenia and osteoporosis (p = 0.0146). However, no differences in BMD were observed with regard to coffee use, alcohol consumption, or smoking. Thus, since the incidence of osteoporosis in IBD patients is high, it may be dependent on PA.     

Aspartame—True or False? Narrative Review of Safety Analysis of General Use in Products

Aspartame is a sweetener introduced to replace the commonly used sucrose. It was discovered by James M. Schlatter in 1965. Being 180–200 times sweeter than sucrose, its intake was expected to reduce obesity rates in developing countries and help those struggling with diabetes. It is mainly used as a sweetener for soft drinks, confectionery, and medicines. Despite its widespread use, its safety remains controversial. This narrative review investigates the existing literature on the use of aspartame and its possible effects on the human body to refine current knowledge. Taking to account that aspartame is a widely used artificial sweetener, it seems appropriate to continue research on safety. Studies mentioned in this article have produced very interesting results overall, the current review highlights the social problem of providing visible and detailed information about the presence of aspartame in products. The studies involving the impact of aspartame on obesity, diabetes mellitus, children and fetus, autism, neurodegeneration, phenylketonuria, allergies and skin problems, its cancer properties and its genotoxicity were analyzed. Further research should be conducted to ensure clear information about the impact of aspartame on health.     

Mesangial expansion at 5 years predicts death and death‐censored graft loss after renal transplantation

Death with a functioning graft and death‐censored renal allograft failure remain major problems for which effective preventative protocols are lacking. The retrospective cohort study aimed to determine whether histologic changes on a 5‐year surveillance kidney biopsy predict adverse outcomes after transplantation in recipients who had: both Type 2 diabetes (T2DM) and obesity (BMI ≥ 30 kg/m²) at the time of transplantation (T2DM/Obesity, n = 75); neither (No T2DM/No obesity, n = 78); No T2DM/Obesity (n = 41), and T2DM/No obesity (n = 47). On 5‐year biopsies, moderate‐to‐severe mesangial expansion was more common in the T2DM/Obesity group (Banff mm score ≥2 = 49.3%; Tervaert classification MS ≥ 2b = 26.7%) compared to the other groups (p < .001 for both scores). Risk factors included older age, higher BMI, HbA1C, and triglycerides at 1‐year post‐transplant. Moderate‐to‐severe mesangial expansion correlated with death with function (HR 1.74 (1.01, 2.98), p = .045 Banff and 1.89 (1.01, 3.51) p = .045 Tervaert) and with death‐censored graft loss (HR 3.2 (1.2, 8.8), p = .02 Banff and HR 3.8 (1.3, 11.5), p = .01 Tervaert) over a mean of 11.6 years of recipient follow‐up post‐transplant. These data suggest that mesangial expansion in recipients with T2DM and obesity may reflect systemic vascular injury and might be a novel biomarker to predict adverse outcomes post renal transplant.     

The impact of COVID-19 and healthcare system changes on the well-being of rheumatic patients

ObjectivesThe COVID-19 pandemic has significantly impacted the healthcare systems. Many Polish outpatient clinics have been implementing telemedical consultations as a tool to ensure the continuity of care for patients with chronic diseases. The aim of the study was to evaluate patients’ satisfaction with telemedical appointments, as well as availability of the various medical services and patients’ well-being during the pandemic.Material and methodsAn online-based questionnaire on the experience with telemedical consultations, availability of medical services and current state of health was conducted among Polish rheumatology patients approximately 6 months after the outbreak of the COVID-19 pandemic.ResultsThe survey was completed by 107 respondents with a mean age of 41.52 ±14.33 years. The overall level of satisfaction from telemedical consultations, evaluated with a VAS 1–10 scale, was assessed as 6.23 ±3.04 for teleconsultations in primary healthcare units and 6.00 ±2.80 for rheumatology outpatient units. 42.99% of the respondents were in favour of maintaining telemedical appointments even after the pandemic. Incidences of reduced access to medical services during the COVID-19 pandemic were reported by 77.57% of the patients. Almost half of the respondents reported reduced accessibility to rheumatological care. An alarming decline in health self-esteem, evaluated with a VAS 1–10 scale, was noted from the average 6.37 ±1.92 before COVID-19 to the current rating of 5.78 ±1.91 (p = 0.0087).ConclusionsPolish rheumatology patients are moderately satisfied with the medical teleconsultations in primary health care units and rheumatology outpatient clinics. A substantial number of patients experienced deterioration of well-being as well as limited access to traditional healthcare services, including rheumatology care.     

Establishing a national HTA program for medical devices in Italy: Overhauling a fragmented system to ensure value and equal access to new medical technologies

Differing contexts have greatly influenced HTA development in various countries, with considerable effort recently made by international HTA networks (e.g., EUnetHTA) and the European Union (EU) to make HTA a more coherent, equal, and efficient process. Medical devices (MDs) present particular challenges for HTA because of frequent, rapid innovation, outcomes influenced by end-user competence, dynamic pricing and often low-quality scientific evidence. Our objective is to describe the development, structure and governance of a National HTA Program for MDs (PNHTADM) in Italy, a highly participatory, stakeholder-engaged, evidence-based process to reform a fragmented system of appraisal and approval. Based largely on EUnetHTA methods, the resulting process delineates a standardized system for proposing MDs by any stakeholders, accrediting HTA producers, setting criteria for prioritization and appraisals, and innovatively linking recommendations with coverage, reimbursement and procurement of MDs. Expected benefits include reduced disparities in pricing and reimbursement policies and improved access to new technologies across 21 regional healthcare systems in Italy's decentralized, universal system, complete with provisions to require additional evidence collection and centrally monitor diffusion. Though devised for Italy, the design, resources and underlying analysis provide a framework for other nations seeking to consolidate HTA initiatives, particularly in light of new EU regulation.     

Dyadic reciprocal associations between self-efficacy and planning predict sedentary behaviour

Objectives

There are two alternative hypotheses regarding bidirectional associations between self-efficacy and planning in predicting health behaviour change: self-efficacy may establish planning (cultivation hypothesis) or planning may enable the formation of self-efficacy (enabling hypothesis). This study investigates the order in which these two social cognitions are linked in adult–adult dyads in the context of sedentary behaviours (SB).

Design

A longitudinal study with 4 measurement points, spanning 8 months.

Methods

A total of 320 dyads (age: 18–90 years) were enrolled. Dyads included a focus person (who received the recommendation to reduce SB and intended to change their SB), and their partners, who were willing to support the focus persons and intended to reduce their own SB as well. Data were collected at Time 1 (T1), Time 2 (1 week later, T2), Time 3 (T3, 2 months after T1) and Time 4 (T4, 8 months after T1). SB was measured with accelerometers at (T1 and T4). Mediation models with individual and dyadic reciprocal effects were tested with path analyses.

Results

Only one indirect effect was found: A higher level of partners' SB reduction-specific self-efficacy at T2 was related to the focus person's more frequent planning to reduce SB at T3, which, in turn, predicted lower SB time among partners at T4.

Conclusions

The findings provide partial support for the cultivation model (self-efficacy prompting planning) and for dyadic reciprocal associations in the context of SB time reduction among adult dyads.     

Isoform selectivity and kinetics of morphine 3- and 6-glucuronidation by human udp-glucuronosyltransferases: evidence for atypical glucuronidation kinetics by UGT2B7.

Morphine elimination involves UDP-glucuronosyltransferase (UGT) catalyzed conjugation with glucuronic acid to form morphine 3- and 6-glucuronides (M3G and M6G, respectively). It has been proposed that UGT2B7 is the major enzyme involved in these reactions, but there is evidence to suggest that other isoforms also catalyze morphine glucuronidation in man. Thus, we have characterized the selectivity and kinetics of M3G and M6G formation by recombinant human UGTs. UGT 1A1, 1A3, 1A6, 1A8, 1A9, 1A10, and 2B7 all catalyzed M3G formation, but only UGT2B7 formed M6G. The kinetics of M3G formation by the UGT1A family isoforms was consistent with a single enzyme Michaelis-Menten model, with apparent Km values ranging from 2.6 to 37.4 mM. In contrast, M3G and M6G formation by UGT2B7 exhibited atypical kinetics. The atypical kinetics may be described by a model with high- and low-affinity Km values (0.42 and 8.3 mM for M3G, and 0.97 and 7.4 mM for M6G) from fitting to a biphasic Michaelis-Menten model. However, a multisite model with an interaction between two identical binding sites in a negative cooperative manner provides a more realistic approach to modeling these data. According to this model, the respective binding affinities (Ks) for M3G and M6G were 1.76 and 1.41 mM, respectively. These data suggest that M6G formation may be used as a selective probe for UGT2B7 activity, and morphine glucuronidation by UGT2B7 appears to involve the simultaneous binding of two substrate molecules, highlighting the need for careful analysis of morphine glucuronidation kinetics in vitro.     

Evaluation of thrombolysis and angioplasty in a porcine iliac artery thrombosis model: application of endovascular stent-graft-induced thrombosis

PURPOSE: To develop a novel endovascular thrombosis model in the porcine iliac artery for the evaluation of thrombolysis and angioplasty. MATERIALS AND METHODS: A stent-inversion-graft (SIG) model combining either a 3-mm or 5-mm tapered expandable polytetrafluoroethylene (ePTFE) graft attached within a self-expandable, 10-mm nitinol stent was placed in the left common iliac artery via an ipsilateral common femoral artery approach in 24 pigs. When the iliac artery was thrombosed, urokinase (250,000 IU) plus heparin (1,000 units) were pulse sprayed via a contralateral femoral approach (n = 12). Saline pulse-spray was used as a control group (n = 12). Balloon angioplasty was performed to eliminate the stenotic tapered graft within the stent after successful thrombolysis. The efficacy of the thrombolysis was assessed with use of intravascular ultrasound (IVUS) and arteriogram. RESULTS: Both the 3-mm tapered and 5-mm tapered SIG models caused iliac artery occlusion in 22 +/- 5 and 41 +/- 9 minutes, respectively, after the deployment. Luminal patency was re-established successfully in all occluded arteries after urokinase infusion. Angioplasty was successful in eliminating the tapered stenosis and restoring the normal diameter in all iliac arteries treated with urokinase. Complete thrombolysis was achieved in both models treated with urokinase. CONCLUSION: This novel endovascular approach of inducing arterial thrombosis is simple to perform and reliably produces arterial thrombosis. The intraluminal stenosis is also amenable to angioplasty. This model is useful for the evaluation of antithrombotic treatment modality and adjunctive endovascular interventions.