Effect of routine MR imaging of the brain at 1.5 T on subsequent magnetoencephalography: results in nine volunteers

PURPOSE: To investigate whether routine magnetic resonance (MR) imaging of the brain with a whole-body 1.5-T imager affects the results of subsequent magnetoencephalography (MEG). MATERIALS AND METHODS: Nine healthy volunteers (six women, mean age of 23 years, age range of 20-27 years; three men, mean age of 24 years, age range of 23-25 years) underwent one MEG session before and two MEG sessions after MR imaging of the brain. The first MEG session was completed about 20 minutes before brain MR imaging began, the second MEG session (MEG 2) was performed within 30 minutes after MR imaging, and the third MEG session was performed 2 hours after MEG 2. Each MEG session involved measurement of spontaneous brain activity and, in seven patients, of brain activity during stimulation of the median nerve. MR imaging included T1- and T2-weighted fast spin-echo and gradient-echo sequences applied with a 1.5-T clinical imager. Data were compared by using a repeated-measures analysis of variance (general linear model) both with and without Greenhouse-Geisser correction. RESULTS: MEG signals were detected and measured without difficulty in all volunteers. No statistically significant difference was seen between estimated noise at MEG before and after MR imaging (P =.588 with correction, P =.665 without correction). MEG records obtained in all volunteers enabled localization of evoked response to median nerve stimulation before and after MR imaging. No measurable differences were observed between relative power spectra of spontaneous brain activity before and after MR imaging (P >.290 with correction, P >or=.295 without correction). CONCLUSION: No measurable effect of 1.5-T brain MR imaging on subsequent MEG was detected.     

Endoscopic lung volume reduction coils for patients with severe emphysema—a single-centre retrospective analysis

 Open in a separate windowOBJECTIVESPatients with chronic obstructive pulmonary disease and lung emphysema may benefit from surgical or endoscopic lung volume reduction (ELVR). Previously reported outcomes of nitinol coil-based ELVR techniques have been ambiguous. The analysis was done to analyse outcomes of ELVR with nitinol coils in patients with severe pulmonary emphysema.METHODSFrom September 2013 to November 2014, our centre performed a total of 41 coil implantations on 29 patients with severe emphysema. Coils were bronchoscopically placed during general anaesthesia. Twelve out of 29 patients received staged contralateral treatments up to 112 days later to avoid bilateral pneumothorax. Lung function and 6-min walking distance were assessed 1 week prior, 1 week after as well as 6–12 months after the procedure. Patients were followed up to 48 months after ELVR and overall mortality was compared to a historic cohort.RESULTSWhile coil-based ELVR led to significant short-term improvement of vital capacity (VC, +0.14 ± 0.39 l, P = 0.032) and hyperinflation (Δ residual volume/total lung capacity −2.32% ± 6.24%, P = 0.022), no significant changes were observed in 6-min walking distance or forced expiratory volume in 1 s. Benefits were short-lived, with only 15.4% and 14.3% of patients showing sustained improvements in forced expiratory volume in 1 s or residual volume after 6 months. Adverse events included haemoptysis (40%) and pneumothorax (3.4%), major complications occurred in 6.9% of cases. Overall survival without lung transplant was 63.8% after 48 months following ELVR, differing insignificantly from what BODE indices of patients would have predicted as median 4-year survival (57%) at the time of ELVR treatment.CONCLUSIONSELVR with coils can achieve small and short-lived benefits in lung function at the cost of major complications in a highly morbid cohort. Treatment failed to improve 4-year overall survival. ELVR coils are not worthwhile the risk for most patients with severe emphysema.     

Management of lung transplantation in the COVID-19 era—An international survey

It is unknown if solid organ transplant recipients are at higher risk for severe COVID-19. The management of a lung transplantation (LTx) program and the therapeutic strategies to adapt the immunosuppressive regimen and antiviral measures is a major issue in the COVID-19 era, but little is known about worldwide practice. We sent out to 180 LTx centers worldwide in June 2020 a survey with 63 questions, both regarding the management of a LTx program in the COVID-19 era and the therapeutic strategies to treat COVID-19 LTx recipients. We received a total of 78 responses from 15 countries. Among participants, 81% declared a reduction of the activity and 47% restricted LTx for urgent cases only. Sixteen centers observed deaths on waiting listed patients and eight centers performed LTx for COVID-19 disease. In 62% of the centers, COVID-19 was diagnosed in LTx recipients, most of them not severe cases. The most common immunosuppressive management included a decreased dose or pausing of the cell cycle inhibitors. Remdesivir, hydroxychloroquine, and azithromycin were the most proposed antiviral strategies. Most of the centers have been affected by the COVID-19 pandemic and proposed an active therapeutic strategy to treat LTx recipients with COVID-19.     

Regulatory T Cell–Derived IL-10 Ameliorates Crescentic GN

Regulatory T cells (Tregs) exert their immunosuppressive activity through several immunoregulatory mechanisms, including the production of anti-inflammatory cytokines such as IL-10. Although several studies suggest a role for Tregs in modulating crescentic GN, the underlying mechanisms are not well understood. Here, using IL-10 reporter mice, we detected IL-10–producing Foxp3⁺ T cells in the kidney, blood, and secondary lymphoid tissue in a mouse model of crescentic GN. Specific inactivation of Il10 in Foxp3⁺ Tregs eliminated the ability of these cells to suppress renal and systemic production of IFNγ and IL-17; these IL-10–deficient Tregs lost their capacity to attenuate renal tissue injury. These data highlight the suppressive functions of Tregs in crescentic GN and suggest the importance of Treg-derived IL-10 in ameliorating disease severity and in modulating both the Th1 and most notably Th17 immune response.The discovery of CD4⁺CD25⁺Foxp3⁺ regulatory T cells (Tregs) in the 1990s and their indispensable role in (self) tolerance and autoimmunity marked the beginning of a new era in immunology.¹ Since then, different suppressive mechanisms mediated by various Treg cell subsets were identified,^2,3 particularly in well studied models of autoimmune diseases such as Crohn''s disease,⁴ multiple sclerosis,⁵ or rheumatoid arthritis.^6,7 Until now, only limited numbers of studies have assessed the function of regulatory T cells in crescentic GN. Adoptive cell transfer experiments in mice showed the beneficial role of exogenous wild-type (wt) CD4⁺CD25⁺ Tregs in attenuation of crescentic GN,⁸ whereas CCR6- and CCR7-deficient CD4⁺CD25⁺ Tregs failed to protect mice against GN.^9,10 Recently, our own published data revealed the importance of endogenous Foxp3⁺ Tregs in suppressing the Th1 immune response and consequently ameliorating the disease severity in the T cell–dependent GN model of nephrotoxic nephritis (NTN).¹¹ Concurrently, Ooi and coworkers confirmed the relevance of endogenous Foxp3⁺ Tregs in an accelerated model of experimental crescentic GN.¹² However, the mechanisms of Treg cell-mediated suppression in crescentic GN are still unclear. One important player might be the anti-inflammatory cytokine IL-10, which is known to be released by Tregs in order to suppress immune responses and therefore might protect against autoimmunity.¹³ Indeed, endogenous IL-10 regulates the Th1 immune response in an accelerated model of experimental crescentic GN, as kidney damage is aggravated in IL-10–deficient mice.¹⁴ However, the source of protective IL-10 still needs to be clarified. Because IL-10 detection and tracking in vivo is difficult, most findings are based on studies with IL-10^−/− mice.Therefore, to study the cell-specific function of IL-10, we used a double-knockin reporter mouse model (Foxp3-IRES-mRFP (FIR) x IL-10 ires gfp-enhanced reporter [tiger]), which enables detection of the well-defined and simultaneous expression of IL-10 (green fluorescent protein [GFP]) and Foxp3 (monomeric red fluorescent protein [mRFP]). Indeed, we detected a distinct population of renal mRFP⁺(Foxp3⁺) Tregs expressing GFP (IL-10) upon induction of NTN. Thus, to investigate the role of Treg cell-derived IL-10 in NTN, we first adoptively transferred CD4⁺CD25⁺ Tregs from wt or IL-10^−/− mice into wt mice subsequently challenged with nephrotoxic sheep serum. Adoptively transferred wt Tregs attenuated the course of NTN, whereas IL-10^−/− Tregs did not. Furthermore, to analyze the role of endogenous IL-10 produced by Tregs, we generated Foxp3^YFP-Cre x Il10^flox/flox mice, in which IL-10 is selectively inactivated in Foxp3⁺ Tregs.¹⁵ Indeed, lack of Treg-derived IL-10 resulted in an aggravated course of NTN. In summary, we demonstrated a crucial role of Treg cell-derived IL-10 in regulating the Th1 and most notably the Th17 immune response in NTN. Hence, this study contributes to the understanding of the suppressive mechanisms of Tregs in crescentic GN and will have biologic implications for designing therapeutic approaches.     

German Association of Endocrine Surgeons practice guideline for the surgical management of malignant thyroid tumors

Introduction

Over the past years, the incidence of thyroid cancer has surged not only in Germany but also in other countries of the Western hemisphere. This surge was first and foremost due to an increase of prognostically favorable (“low risk”) papillary thyroid microcarcinomas, for which limited surgical procedures are often sufficient without loss of oncological benefit. These developments called for an update of the previous practice guideline to detail the surgical treatment options that are available for the various disease entities and tumor stages.

Methods

The present German Association of Endocrine Surgeons practice guideline was developed on the basis of clinical evidence considering current national and international treatment recommendations through a formal expert consensus process in collaboration with the German Societies of General and Visceral Surgery, Endocrinology, Nuclear Medicine, Pathology, Radiooncology, Oncological Hematology, and a German thyroid cancer patient support organization.

Results

The practice guideline for the surgical management of malignant thyroid tumors includes recommendations regarding preoperative workup; classification of locoregional nodes and terminology of surgical procedures; frequency, clinical, and histopathological features of occult and clinically apparent papillary, follicular, poorly differentiated, undifferentiated, and sporadic and hereditary medullary thyroid cancers, thyroid lymphoma and thyroid metastases from primaries outside the thyroid gland; extent of thyroidectomy; extent of lymph node dissection; aerodigestive tract resection; postoperative follow-up and surgery for recurrence and distant metastases.

Conclusion

These evidence-based recommendations for surgical therapy reflect various “treatment corridors” that are best discussed within multidisciplinary teams and the patient considering tumor type, stage, progression, and inherent surgical risk.     

EUROSPINE 2016 FULL PAPER AWARD: Wire cerclage can restore the stability of the thoracic spine after median sternotomy: an in vitro study with entire rib cage specimens

Purpose

The influence of the anterior rib cage on the stability of the human thoracic spine is not completely known. One of the most common surgical interventions on the anterior rib cage is the longitudinal median sternotomy and its fixation by wire cerclage. Therefore, the purpose of this in vitro study was to examine, if wire cerclage can restore the stability of the human thoracic spine after longitudinal median sternotomy.

Methods

Six fresh frozen human thoracic spine specimens (C7–L1, 56 years in average, range 50–65), including the intact rib cage without intercostal muscles, were tested in a spinal loading simulator and monitored with an optical motion tracking system. While applying 2 Nm pure moment in flexion/extension (FE), lateral bending (LB), and axial rotation (AR), the range of motion (ROM) and neutral zone (NZ) of the functional spinal units of the thoracic spine (T1–T12) were studied (1) in intact condition, (2) after longitudinal median sternotomy, and (3) after sternal closure using wire cerclage.

Results

The longitudinal median sternotomy caused a significant increase of the thoracic spine ROM relative to the intact condition (FE: 12° ± 5°, LB: 18° ± 5°, AR: 25° ± 10°) in FE (+12 %) and AR (+22 %). As a result, the sagittal cut faces of the sternum slipped apart visibly. Wire cerclage fixation resulted in a significant decrease of the ROM in AR (?12 %) relative to condition after sternotomy. ROM increased relative to the intact condition, in AR even significantly (+8 %). The NZ showed a proportional behavior compared to the ROM in all loading planes, but it was distinctly higher in FE (72 %) and in LB (82 %) compared to the ROM than in AR (12 %).

Conclusions

In this in vitro study, the longitudinal median sternotomy resulted in a destabilization of the thoracic spine and relative motion of the sternal cut faces, which could be rectified by fixation with wire cerclage. However, the stability of the intact condition could not be reached. Nevertheless, a fixation of the sternum should be considered clinically to avoid instability of the spine and sternal pseudarthrosis.

     

Simvastatin does not prevent acute cardiac allograft rejection in CD28-deficient mice

Background  

Heterotopic cardiac transplantation in mice was used to determine whether complementary immunomodulation by statins prevents lymphocyte function-associated antigen (LFA)-1-dependent acute allograft rejection in vivo.