Conventional Total Thyroidectomy Using a Novel Single Retractor: Technical Note for Apollo®.

Despite the increasingly innovative techniques developed in thyroid surgery to offer patients minimally invasive and scarless interventions, conventional open procedures still account for most of the interventions performed in this field. The surgical incision length has been significantly reduced, from 6-9 cm to 3 cm, and therefore patients perceive the scar to be highly acceptable. In this technical note, we present the use of a new single retractor (APOLLO®; AFS MEDICAL GmbH, Teesdorf, Austria) for conventional open thyroidectomies with intraoperative neuromonitoring. This device offers several advantages: a) better exposure of the surgical field; b) less traction on skin flaps and neck muscles; and c) protection of the skin edges from the heat generated by energy-based devices/coagulating instruments, with consequent better healing.

miR-7 Regulates GLP-1-Mediated Insulin Release by Targeting ß-Arrestin 1.

Glucagon-like peptide-1 (GLP-1) has been shown to potentiate glucose-stimulated insulin secretion binding GLP-1 receptor on pancreatic ß cells. ß-arrestin 1 (ßARR1) is known to regulate the desensitization of GLP-1 receptor. Mounting evidence indicates that microRNAs (miRNAs, miRs) are fundamental in the regulation of ß cell function and insulin release. However, the regulation of GLP-1/ßARR1 pathways by miRs has never been explored. Our hypothesis is that specific miRs can modulate the GLP-1/ßARR1 axis in ß cells. To test this hypothesis, we applied a bioinformatic approach to detect miRs that could target ßARR1; we identified hsa-miR-7-5p (miR-7) and we validated the specific interaction of this miR with ßARR1. Then, we verified that GLP-1 was indeed able to regulate the transcription of miR-7 and ßARR1, and that miR-7 significantly regulated GLP-1-induced insulin release and cyclic AMP (cAMP) production in ß cells. Taken together, our findings indicate, for the first time, that miR-7 plays a functional role in the regulation of GLP-1-mediated insulin release by targeting ßARR1. These results have a decisive clinical impact given the importance of drugs modulating GLP-1 signaling in the treatment of patients with type 2 diabetes mellitus.

Exercise related ventilation dynamics and clinical correlates in patients with fibrotic idiopathic interstitial pneumonias.

Assessment of exercise performance is a key component in the management of interstitial lung diseases, as its limitation may occur very early. Aim of the present study was to assess ventilation dynamics in combination with pulse-oximetry changes in 54 clinically stable patients affected by idiopathic pulmonary fibrosis or idiopathic fibrotic nonspecific interstitial pneumonia. Testing was successfully performed with the Spiropalm 6-MWT Hand-held spirometer by the majority of cases (94%). End test oxygen saturation (SpO2) values <88% were common in most of patients (76%), with a mean distance walked of 403 meters. Ventilation significantly increased due to the contribution of the tidal volume and the respiratory frequency (RF). This finding was associated with a decrease of the end of test respiratory reserve (RR), that was <20% in 9 cases (17.6%). Lung function was inversely related to the end of test RF, while a positive correlation occurred with the end of test RR and the estimated maximal voluntary ventilation (MVV). RR was also a predictive factor of declining forced vital capacity and lung diffusion capacity for carbon monoxide (DLCO) over a 6-month period. Further factors of DLCO impairment were low SpO2 and MVV. Comparison with the cardio-pulmonary exercise test (CPET) showed that the 6-MWT end of test RR was inversely related to the CPET-derived peak RF and VE/VCO2 suggesting RR as pivotal in exercise limitation assessment. Our results open challenging perspectives in an unexplored field. Future research will include management of latent respiratory failure and monitoring of disease progression and therapy response.

Current treatment options for latent tuberculosis infection.

Treatment of latent tuberculosis infection (LTBI) is a key component in TB control strategies worldwide. However, as people with LTBI are neither symptomatic nor contagious, any screening decision should be weighed carefully against the potential benefit of preventing active disease in those who are known to be at higher risk and are willing to accept therapy for LTBI. This means that a targeted approach is desirable to maximize cost effectiveness and to guarantee patient adherence. We focus on LTBI treatment strategies in patient populations at increased risk of developing active TB, including candidates for treatment with tumor necrosis factor-α blockers. In the last 40 years, isoniazid (INH) has represented the keystone of LTBI therapy across the world. Although INH remains the first therapeutic option, alternative treatments that are effective and associated with increased adherence and economic savings are available. Current recommendations, toxicity, compliance, and cost issues are discussed in detail in this review. A balanced relationship between the patient and healthcare provider could increase adherence, while cost-saving treatment strategies with higher effectiveness, fewer side effects, and of shorter duration should be offered as preferred.

The use of TNF-α blockers in psoriatic arthritis patients with latent tuberculosis infection.

Psoriatic arthritis (PsA) is an inflammatory arthropathy associated with skin and/or nail psoriasis. TNF-α is an essential cytokine for the host defense, and its depletion by treatment may facilitate the risk of infections or their reactivation. The aim of this study was to evaluate the efficacy and safety of TNF-α blockers in patients with PsA and concomitant latent tuberculosis infection (LTBI) comparing their outcome with non-infected PsA patients. This is a retrospective study in 321 patients with PsA, attending the Psoriatic Arthritis Clinic at the University Federico II of Naples, who had an inadequate response to DMARDs and started therapy with TNF-α blockers. We identified 40 patients with LTBI, who were included in this study along with 40 not infected PsA patients as control group. At baseline (T0) and every 3 months for 2 years (T2), data concerning PsA activity were registered. All patients underwent chest X-ray every 6 months (or 12 if appropriate). In each group, 22 patients were on etanercept therapy, 14 on adalimumab, and 4 on infliximab. Anti-TNF-α therapy was effective in both group of patients, and no statistically significant differences were found in the analysis of the study variables between the two groups from T0 to T2. No serious adverse events occurred in both groups, and no patient was withdrawn from therapy. Our experience suggests that anti-TNF-α treatment is effective and safe in PsA patients with concomitant LTBI. Therefore, neither LTBI nor chemoprophylaxis seems to influence the course of anti-TNF-α therapy.

Screening and monitoring of latent tubercular infection in patients taking tumor necrosis factor-α blockers for psoriatic arthritis.

Patients with arthritis who need treatment with biologics are carefully screened for possible previous exposure to tuberculosis to detect any latent tubercular infection (LTBI). The traditional method of screening for LTBI is not specific, because positivity could also depend on infection by atypical mycobacteria and bacillus Calmette-Guerin vaccination. In addition, the screening does not show high sensitivity, frequently presenting a false negativity because of immunosuppression caused by drugs used for arthritis. Recently, interferon-γ release assays (IGRA) have been used to screen LTBI with more sensitivity and specificity before treatment with anti-tumor necrosis factor-α drugs. Moreover, in our experience, IGRA are potentially useful in monitoring LTBI during biologic therapy.

Angiogenesis in chronic obstructive pulmonary disease: a translational appraisal.

Angiogenesis is a crucial component of lung pathophysiology, not only in cancer but also in other disorders, such as chronic obstructive pulmonary disease (COPD). In COPD angiogenesis is definitely able to control and orchestrate the progression of airway remodeling. Herein, we provide several remarkable translational aspects of angiogenesis in COPD, exploring both basic and clinical research in this field. Indeed, we present a number of pro- and anti-angiogenic factors, which can be also used as potential biomarkers to monitor disease progression.

Prevention of tuberculosis in patients taking tumor necrosis factor-alpha blockers.

Treatment with tumor necrosis factor-alpha (TNF-alpha) inhibitors increases the risk of tuberculosis (TB) due to reactivation of latent Mycobacterium tuberculosis infection (LTBI). Screening for LTBI is based mainly on the tuberculin skin test (TST), which has several limitations in any patient who is immunosuppressed due to drugs or autoimmune disease. T cell interferon-gamma release assays (IGRA) have been shown to be more specific than TST in immunocompetent patients and potentially represent a new approach for the management of patients taking TNF-alpha blockers. Even if there is no evidence-based literature of IGRA superiority versus TST in this specific clinical setting, some studies suggest blood assays may be helpful in clinical management of these patients, in addition to currently recommended clinical screening for risk factors for LTBI.

IFN-gamma release assays in tuberculosis management in selected high-risk populations.

Tuberculosis (TB) is the most deadly infectious disease in the world. TB control relies on passive case findings and targeted treatment of latently infected individuals at high risk of disease progression. Tuberculin skin testing (TST) is conventionally used for detection of TB infection. Recently, blood assays measuring the release of IFN-gamma by TB-specific effector memory T cells have been developed to overcome TST limitations. Overall, IFN-gamma release assays are more specific than TST, more sensitive in detecting active TB and correlate better with TB exposure in immune-competent patients, at least in low-burden settings. There are three US FDA-approved assays commercially available: the ELISpot-based assay T-SPOT.TB (Oxford Immunotech, UK) and two ELISA-based formats, QuantiFERON TB Gold (QFT) and QFT-in tube (Cellestis, Australia). Recent international guidelines and consensus statements recommend the use of IFN-gamma release assays at different levels in TB management. However, conclusive evidence-based information targeting populations at high TB risk, including HIV-infected individuals, children and patient candidates for biotherapy with TNF-alpha blockers, are lacking. The aim of this review is to focus our attention on studies addressing the performance of commercial IFN-gamma release assays in clinical management of TB infection in these highly selected settings to provide a more comprehensive picture of the actual scenario and to identify areas to be investigated further.