Revisiting serum thyroglobulin in the follow-up of patients with differentiated thyroid carcinoma

This study analyzed serum thyroglobulin (Tg) during hypothyroidism in 207 patients with differentiated thyroid carcinoma treated with total thyroidectomy and radioiodine ablation and undetectable anti-Tg antibodies. Disease staging was defined by clinical examination, stimulated Tg, pre- and post-ablative radioiodine scanning, and other imaging methods (X-Ray, US, CT and MIBI-scan). The average interval from initial therapy was 2.3 years. 153 patients (74%) had no evident disease, 34 (16.4%) presented neck/mediastinal disease, and 20 (9.6%) had distant metastases (Mt). The best cut-off for Tg was 1 ng/ml, showing 100% sensitivity for distant Mt and 88.2% for local recurrence or lymph node Mt, and 88.8% specificity for any Mt and 74.8% for distant Mt. In patients with Tg <1 ng/ml, 2.8% showed cervical lymph nodes Mt. Cervical or mediastinal disease were 26% of cases with Tg between 1 and 5 ng/ml. Tg from 5 to 10 ng/ml was associated to distant Mt in 14.2% of the cases and others showed lymph nodes Mt. In patients with Tg >10 ng/ml, 51.3% presented distant Mt. We suggest the need for neck US even in cases with Tg <1 ng/ml. In addition, patients with Tg levels <5 ng/ml should be investigated by neck US and mediastinal CT only, and empirical therapy should be limited to patients with a minimum Tg level >5 ng/ml.     

Increased Contextual Fear Conditioning in iNOS Knockout Mice: Additional Evidence for the Involvement of Nitric Oxide in Stress-Related Disorders and Contribution of the Endocannabinoid System

Background:

Inducible or neuronal nitric oxide synthase gene deletion increases or decreases anxiety-like behavior in mice, respectively. Since nitric oxide and endocannabinoids interact to modulate defensive behavior, the former effect could involve a compensatory increase in basal brain nitric oxide synthase activity and/or changes in the endocannabinoid system. Thus, we investigated the expression and extinction of contextual fear conditioning of inducible nitric oxide knockout mice and possible involvement of endocannabinoids in these responses.

Methods:

We evaluated the effects of a preferential neuronal nitric oxide synthase inhibitor, 7-nitroindazol, nitric oxide synthase activity, and mRNA changes of nitrergic and endocannabinoid systems components in the medial prefrontal cortex and hippocampus of wild-type and knockout mice. The effects of URB597, an inhibitor of the fatty acid amide hydrolase enzyme, which metabolizes the endocannabinoid anandamide, WIN55,212-2, a nonselective cannabinoid agonist, and AM281, a selective CB1 antagonist, on contextual fear conditioning were also evaluated.

Results:

Contextual fear conditioning expression was similar in wild-type and knockout mice, but the latter presented extinction deficits and increased basal nitric oxide synthase activity in the medial prefrontal cortex. 7-Nitroindazol decreased fear expression and facilitated extinction in wild-type and knockout mice. URB597 decreased fear expression in wild-type and facilitated extinction in knockout mice, whereas WIN55,212-2 and AM281 increased it in wild-type mice. Nonconditioned knockout mice showed changes in the mRNA expression of nitrergic and endocannabinoid system components in the medial prefrontal cortex and hippocampus that were modified by fear conditioning.

Conclusion:

These data reinforce the involvement of the nitric oxide and endocannabinoids (anandamide) in stress-related disorders and point to a deregulation of the endocannabinoid system in situations where nitric oxide signaling is increased.     

The use of minimal fluoroscopy for cardiac electrophysiology procedures: A meta‐analysis and review of the literature

BackgroundConventional catheter ablation involves prolonged exposure to ionizing radiation, potentially leading to detrimental health effects. Minimal fluoroscopy (MF) represents a safer alternative, which should be explored. Data on the safety and efficacy of this technique are limited.HypothesisOur hypothesis is that MF is of equal efficacy and safety to conventional catheter ablation with the use of fluoroscopy by performing a meta‐analysis of both randomized controlled trials (RCTs) and real‐world registry studies.MethodsPubmed and Embase were searched from their inception to July 2020 for RCTs, cohort and observational studies that assessed the outcomes of catheter ablation using a MF technique versus the conventional approach.ResultsFifteen studies involving 3795 patients were included in this meta‐analysis. There was a significant reduction in fluoroscopy and procedural time with no difference in acute success (odds ratio [OR]:0.74, 95% CI: 0.50–1.10, p = .14), long‐term success (OR:0.92, 95% CI: 0.65–1.31, p = .38), arrhythmia recurrence (OR:1.24, 95% CI: 0.75–2.06, p = .97) or rate of complications. (OR:0.83, 95% CI: 0.46–1.48, p = .65). Additionally sub‐group analysis for those undergoing catheter ablation for atrial fibrillation (AF) did not demonstrate a difference in success or complication rates (OR:0.86, 95% CI: 0.30–2.42, p = .77). Multivariate meta‐regression did not identify the presence of moderator variables.ConclusionThis updated meta‐analysis demonstrated an overall reduction in procedural and fluoroscopy time for those undergoing a minimal fluoroscopic approach. There was no significant difference in either acute or chronic success rates or complications between a MF approach and conventional approach for the management of all arrhythmias including those undergoing catheter ablation for AF.     

Increased Risk of Infections with Anti-TNF Agents in Patients with Crohn’s Disease After Elective Surgery: Meta-Analysis

Digestive Diseases and Sciences - Postoperative complication rates in patients with inflammatory bowel disease (IBD) receiving preoperative biologics have been analyzed without considering the...     

The influence of the crutch setup on stability and weight-bearing parameters in post total hip replacement surgery patients during quiet standing

Purpose: The purpose of this study is to evaluate the influence of the crutch setup on standing, in post total hip replacement (THR) surgery patients.

Materials and methods: Thirty patients after THR were randomly assigned to walking with the elbow flexed (EF) or elbow straight (ES) crutch setup. Subjects were asked to stand on a force platform in a comfortable position with the crutch positioned on the unaffected side, facing forward for 10?seconds. Centre of pressure total path and maximal excursion were evaluated in both medio-lateral and anterior–posterior planes. Difference in the asymmetry of left/right acromial height, measured with and without the crutch, was calculated (ACdiff). Percentage of body weight borne by the crutch (Fcr), symmetry (SIload) between operated and healthy limbs loading during the trial, together with shoulder forces and moments were measured.

Results: No significant differences between the two groups (p?>?.05) were found for stability parameters. ACdiff, Fcr and shoulder load increased significantly (p?Conclusions: The present study showed that the ES setup reduced the force borne by the crutch, the load on the shoulder joint and it minimized postural and loading asymmetries when compared to EF setup. Conversely, postural stability was not influenced by the crutch setup.

• Implications for Rehabilitation

• Static posture and weight-bearing parameters are influenced by crutch setup during quiet standing.

• Crutch setup does not influence postural stability.

• Adjusting the crutch according to the elbow straight setup reduces the force borne by the crutch and the asymmetry in lower limbs loading.

• Forces and moments at the shoulder joint were reduced for the elbow straight setup group.

     

Exercise training improves the IL-10/TNF-α cytokine balance in the gastrocnemius of rats with heart failure

Objective

This study examined the effects of exercise training (ExT) upon concentration of tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6) and interleukin-10 (IL-10) in the gastrocnemius of rats with heart failure (HF) induced by left coronary artery ligation.

Can demographic and anthropometric characteristics predict clinical improvement in patients with chronic non-specific low back pain?

Objective

To identify potential prognostic factors that may predict clinical improvement of patients treated with different physical therapy interventions in the short-term.

Molecular diagnosis of coenzyme Q10 deficiency: an update

Introduction: Coenzyme Q₁₀ (CoQ) deficiency syndromes comprise a growing number of genetic disorders. While primary CoQ deficiency syndromes are rare diseases, secondary deficiencies have been related to both genetic and environmental conditions, which are the main causes of biochemical CoQ deficiency. The diagnosis is the essential first step for planning future treatment strategies, as the potential treatability of CoQ deficiency is the most critical issue for the patients.

Areas covered: While the quickest and most effective tool to define a CoQ-deficient status is its biochemical determination in biological fluids or tissues, this quantification does not provide a definite diagnosis of a CoQ-deficient status nor insight about the genetic etiology of the disease. The different laboratory tests to check for CoQ deficiency are evaluated in order to choose the best diagnostic pathway for the patient.

Expert commentary: New insights are being discovered about the implication of new proteins in the intricate CoQ biosynthetic pathway. These insights reinforce the idea that next generation sequencing diagnostic strategies are the unique alternative in terms of rapid and accurate molecular diagnosis of CoQ deficiency.     

Exploratory evaluation of pharmacodynamics,pharmacokinetics and safety of rivaroxaban in children and adolescents: an EINSTEIN-Jr phase I study

Background

The EINSTEIN-Jr program will evaluate rivaroxaban for the treatment of venous thromboembolism (VTE) in children, targeting exposures similar to the 20 mg once-daily dose for adults.

Methods

This was a multinational, single-dose, open-label, phase I study to describe the pharmacodynamics (PD), pharmacokinetics (PK) and safety of a single bodyweight-adjusted rivaroxaban dose in children aged 0.5–18 years. Children who had completed treatment for a venous thromboembolic event were enrolled into four age groups (0.5–2 years, 2–6 years, 6–12 years and 12–18 years) receiving rivaroxaban doses equivalent to 10 mg or 20 mg (either as a tablet or oral suspension). Blood samples for PK and PD analyses were collected within specified time windows.

Results

Fifty-nine children were evaluated. In all age groups, PD parameters (prothrombin time, activated partial thromboplastin time and anti-Factor Xa activity) showed a linear relationship versus rivaroxaban plasma concentrations and were in line with previously acquired adult data, as well as in vitro spiking experiments. The rivaroxaban pediatric physiologically based pharmacokinetic model, used to predict the doses for the individual body weight groups, was confirmed. No episodes of bleeding were reported, and treatment-emergent adverse events occurred in four children and all resolved during the study.

Conclusions

Bodyweight-adjusted, single-dose rivaroxaban had predictable PK/PD profiles in children across all age groups from 0.5 to 18 years. The PD assessments based on prothrombin time and activated partial thromboplastin time demonstrated that the anticoagulant effect of rivaroxaban was not affected by developmental hemostasis in children.

Trial registration

ClinicalTrials.gov number, NCT01145859.

     

Treatment of Helicobacter pylori infection: A clinical practice update

Background

Helicobacter pylori infection is still frequent in the community and all infected subjects should be offered an eradication therapy. Nowadays physicians have to face the challenge of antibiotic resistance in treating Helicobacter pylori‐infected individuals.

Aim

This review provides an overview of current international guidelines and reports recent evidence from systematic reviews and clinical trials on the treatment of Helicobacter pylori infection and should help physicians to better treat their patients.

Results

General rules to optimize the management of Helicobacter pylori infection include: (i) considering previous patient's exposure to antibiotics; (ii) using high dose of proton‐pump inhibitors; and (iii) avoiding repeating the same regimen, if it has already failure. Bismuth quadruple therapy and concomitant therapy are the best first‐line empirical treatments in areas with high clarithromycin resistance and in individuals with previous use of macrolides; otherwise, the 14‐day clarithromycin‐containing triple therapy is a valid regimen. The sequential therapy is no longer a suggested treatment by international guidelines.

Conclusions

Current international guidelines are consistent in defining treatment strategies for Helicobacter pylori infection. The use of national registries to monitor the efficacy and tolerability of different regimens in the real world of clinical practice is now needed.