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Background: The aim of this study was to evaluate the effect of a single early administration of dexamethasone and escin after loss of signal (LOS) during a neuromonitored total thyroidectomy. Methods: A retrospective analysis of results concerning consecutive patients undergoing total thyroidectomy was performed. Patients included in the study were divided into two groups: Group 1 for which a “wait and see” strategy was used; Group 2, receiving dexamethasone and escin immediately after LOS detection. Results: Overall 37 patients were included in Group 1 and 35 in Group 2. LOS recovery occurring in 29.7% of cases (n. 11) versus 65.7% (n. 23) respectively (p < 0.001). Postoperative fibrolayngoscopy for patients without LOS recovery showed normal cord function in 4 out of 26 cases (15.4%) in Group 1 and in 7 out of 12 (58.3%) in Group 2 (p < 0.001). Conclusions: The early administration of dexamethasone and escin after LOS detection may achieve greater EMG signal recovery than a “wait and see” strategy.

Purpose Local neck symptoms (LNS) may be related to goiter, but are also reported by patients suffering from laryngeal–pharyngeal reflux (LPR). The aim of this study was to investigate whether LPR could play a role in the persistence of some LNS after total thyroidectomy (TT). Methods A consecutive case series of 160 patients with multinodular goiter (MNG) candidate for TT were included in this study. Each patient was closely studied for both the thyroid pathology and reflux disease before and 6 months after surgery to assess the persistence of LNS after surgery. Results Only throat discomfort showed a significant improvement (p = 0.031) after surgery. On the other hand, swallowing and voice disorders persisted after surgery in 82.3% and 77.3% of patients, respectively (p = 0.250 and p = 0.062), such as the correlated reflux laryngopharyngitis (p = 0.5). Conclusions LPR can be considered a predisposing factor or an important concurrent causa to the persistence of LNS after TT, in particular for swallowing disorders and voice disorders. In patients with non-toxic MNG who complain of local neck symptoms, the investigation of a possible coexistence of a reflux disease is appropriate before surgery. Patients should be informed about the possibility that some symptoms can persist even after removal of the goiter.

Mushroom extracts are a rich source of natural compounds with antimicrobial properties, which are able to prevent, to some extent, the growth of foodborne pathogens. The aim of this study was to investigate the potential of extracts from albino Grifola frondosa (GF), commonly known as maitake, to inhibit the growth of some bacteria and the biofilm production by Staphylococcus aureus. We obtained not only a significant reduction of OD score between biofilm and biofilm plus albino G. frondosa extract group, but also a reduction of category of biofilm. In addition, we observed a significant presence of isolates with strong category for the biofilm group and a significant presence of isolates with absent category for the biofilm plus albino G. frondosa extract group. These results confirm that the use of albino G. frondosa extract reduces in significant way the presence of biofilm. Our results suggest and confirm that albino G. frondosa extracts could be employed as functional food and could be used as a natural additive for food process control and food safety.

Background Sentinel lymph node biopsy is the gold standard surgical technique for axillary staging in patients with clinically node-negative. However, it is still uncertain what is the optimal number of sentinel lymph nodes (SLNs) to be removed to reduce the false-negative rate. The aim of this study was to investigate whether patients with a single negative SLN have a worse prognosis than those with two or more negative SLNs. Methods A retrospective review was conducted on a large series of SLN-negative breast cancer patients. Survival outcomes and regional recurrence rate were evaluated according to the number of removed SLNs. Secondly, the contribution of different adjuvant therapies on disease-free survival was explored. Statistical analysis included the chi-square, Wilcoxon–Mann–Whitney test, and Kaplan–Meier survival analysis. Results A total of 1080 patients were included in the study. A first group consisted of 328 patients in whom a single SLN was retrieved, and a second group consisted of 752 patients in whom two or more SLNs were retrieved. There was no relevant difference in median DFS (64.9 vs 41.4) for SLN = 1 vs SLN > 1 groups (HR 0.76, CI 95% 0.39–1.46; p = 0.38). A statistically significant difference in mDFS was showed only for HT-treated patients who were SLN = 1 if compared to SLN > 1 (100.6 months versus 35.3 months). Conclusions There is likely a relationship between the number of resected SNL and mDFS. Our results, however, showed no relevant difference in median DFS for SLN = 1 vs SLN > 1 group, except for a subset of the patients treated with hormone therapy.

Background The aim of this study was to evaluate the reliability of intraoperative neuromonitoring through recurrent laryngeal nerve stimulation and simultaneous laryngeal palpation (NSLP) in predicting postoperative vocal cord palsy and in providing useful information in the decision to perform a staged surgery in initially planned total thyroidectomy. Materials and Methods A retrospective review was performed involving 552 patients for whom a total thyroidectomy was planned. In all patients, preoperative and postoperative laryngoscopy was performed. The incidence of vocal cord palsy was calculated on 1104 nerves at risk. Results Sensitivity and specificity of NSLP were 0.9411 and 0.9925 respectively. The positive predictive value was 0.7804, the negative predictive value was 0.9981, the false positive rate was 0.8%. In 41 patients (7.4%) the initial surgical strategy was changed into a staged procedure. Nine patients (21.9%) were false positive, 32 patients (78.1%) were true positive. Finally, a two-stage thyroidectomy was performed in 27 of 41 patients. Conclusions High sensitivity and specificity confirm the validity of NSLP in predicting postoperative vocal cord palsy and in driving a possible staged thyroidectomy, both in benign thyroid disease and in differentiated thyroid carcinoma.

LetB is a tunnel-forming protein found in the cell envelope of some double-membraned bacteria, and is thought to be important for the transport of lipids between the inner and outer membranes. In Escherichia coli the LetB tunnel is formed from a stack of seven rings (Ring1 - Ring7), in which each ring is composed of a homo-hexameric assembly of MCE domains. The primary sequence of each MCE domain of the LetB protein is substantially divergent from the others, making each MCE ring unique in nature. The role of each MCE domain and how it contributes to the function of LetB is not well understood. Here we probed the importance of each MCE ring for the function of LetB, using a combination of bacterial growth assays and cryo-EM. Surprisingly, we find that ΔRing3 and ΔRing6 mutants, in which Ring3 and Ring6 have been deleted, confer increased resistance to membrane perturbing agents. Specific mutations in the pore-lining loops of Ring6 similarly confer increased resistance. A cryo-EM structure of the ΔRing6 mutant shows that despite the absence of Ring6, which leads to a shorter assembly, the overall architecture is maintained, highlighting the modular nature of MCE proteins. Previous work has shown that Ring6 is dynamic and in its closed state, may restrict the passage of substrate through the tunnel. Our work suggests that removal of Ring6 may relieve this restriction. The deletion of Ring6 combined with mutations in the pore-lining loops leads to a model for the tunnel gating mechanism of LetB. Together, these results provide insight into the functional roles of individual MCE domains and pore-lining loops in the LetB protein.HighlightsDeleting MCE domains 3 or 6 from LetB confers increased resistance to membrane-perturbing agentsCryo-EM structure of ΔRing6 LetB mutant highlights the modular nature of MCE domainsMutations along LetB pore-lining loops modulate detergent resistance

Obesity is a strong risk factor for cancer progression, posing obesity-related cancer as one of the leading causes of death. Nevertheless, the molecular mechanisms that endow cancer cells with metastatic properties in patients affected by obesity remain unexplored. Here, we show that IL-6 and HGF, secreted by tumor neighboring visceral adipose stromal cells (V-ASCs), expand the metastatic colorectal (CR) cancer cell compartment (CD44v6 + ), which in turn secretes neurotrophins such as NGF and NT-3, and recruits adipose stem cells within tumor mass. Visceral adipose-derived factors promote vasculogenesis and the onset of metastatic dissemination by activation of STAT3, which inhibits miR-200a and enhances ZEB2 expression, effectively reprogramming CRC cells into a highly metastatic phenotype. Notably, obesity-associated tumor microenvironment provokes a transition in the transcriptomic expression profile of cells derived from the epithelial consensus molecular subtype (CMS2) CRC patients towards a mesenchymal subtype (CMS4). STAT3 pathway inhibition reduces ZEB2 expression and abrogates the metastatic growth sustained by adipose-released proteins. Together, our data suggest that targeting adipose factors in colorectal cancer patients with obesity may represent a therapeutic strategy for preventing metastatic disease., Obesity is a major risk factor for cancer related death. Here, the authors show that visceral adipose-derived factors promote vasculogenesis and metastatic dissemination by activation of STAT3, which inhibits miR-200a and enhances ZEB2 expression, effectively reprogramming colorectal cancer cells into a highly metastatic phenotype.

Background The association between Hashimoto’s thyroiditis (HT) and papillary thyroid carcinoma (PTC) is a controversial question that is still under debate, its pathological significance and the eventual clinical implications of this association remaining unclear. Methods The data regarding 305 patients were retrospectively analyzed. The patients were divided in two different groups. A first group made up of 142 patients undergoing surgery for differentiated thyroid carcinoma was compared to a control group of 142 analogous subjects operated for normofunctioning goiter. A second group was made up of 163 patients who had undergone total thyroidectomy (TT) with pre-operative diagnosis of HT. Results In the first group of patients an association with HT was found in 28,6% of the patients with final histopathological diagnosis of PTC versus 7,7% of the patients with histopathological diagnosis of multinodular goiter, which was a significant difference (p

Background/Aim: The aim of this study was to evaluate the current role of frozen section in identifying patients who could benefit from an immediate axillary lymph node dissection (ALND), following the criteria of the ASOCOG Z0011 and IBCSG 23-10 trials. Patients and Methods: A retrospective review was performed involving 2,079 patients with early breast cancer who underwent conservative surgery or total mastectomy with sentinel lymph node biopsy. Results: Sensitivity and diagnostic accuracy were 63.8% and 90.3%, respectively. Sensitivity was significantly higher (p

Background The accuracy of axillary ultrasound (AUS) with fine-needle aspiration with varying patient body mass index (BMI) is still unclear. The aim of our study was to evaluate whether the US features of axillary lymph nodes changes with BMI of patients. Patients and methods A retrospective review was performed involving 144 out of 270 patients with early breast cancer who underwent breast surgery with sentinel lymph node biopsy. Diagnostic efficacy of AUS in preoperative axillary nodal staging was assessed in relation to BMI. Results Negative predictive values of AUS for the overweight and obese groups were statistically significantly lower compared to the normal/underweight group (p=0.02 and p=0.003, respectively). Additionally, Spearman's correlation coefficient R between BMI and positive sentinel lymph node biopsy was 0.257, suggesting a significantly positive linear relationship between the two variables in the cohort overall. Conclusion Our results demonstrate how in our cohort the negative predictive value of AUS was significantly influenced by adipose tissue and that the selection of the most suitable instrumental diagnostic technique might contribute to improving heterogeneous results.

BACKGROUND/AIM: Recent years have seen a considerable shift to a more conservative management of the axilla in patients with positive axillary sentinel lymph nodes. The aim of this study was to determine whether some breast cancer patients with a preoperative ultrasound-guided needle aspiration biopsy proven positive node could potentially be spared an axillary lymph node dissection according to the ACOSOG Z0011 trial criteria. PATIENTS AND METHODS: A retrospective review was performed involving 623 breast cancer patients who underwent axillary lymph node dissection after either ultrasound-guided needle aspiration biopsy proven positive node or sentinel lymph node biopsy. RESULTS: Patients with fine needle aspiration biopsy-proven positive node had worse prognosis and a higher nodal burden (6.7 vs 1.9 nodes, p

Inflammatory bowel disease (IBD) remains a global health problem with a significant percentage of patients progressing to chronic inflammation and colitis-associated cancer (CAC). Whether or not γδ T cells contribute to initiation and maintenance of inflammation in IBD and in the development of CAC is not known. We have evaluated the frequency, phenotype, and functions of γδ T cells among tissue-infiltrating lymphocytes in healthy donors and IBD and CAC patients. Results show that Vδ1 T cells are the dominant γδ T-cell population in healthy tissue, whereas Vδ2 T significantly abound in chronic IBD. Vδ2 T cells produce more IFN-γ, TNF-α, and IL-17 than Vδ1 T cells in chronic inflamed IBD. In CAC patients no significant cytokine production was detected in tissue-resident Vδ1 T cells, but Vδ2 T cells produced remarkable amounts of IFN-γ and TNF-α; these data were confirmed by the analysis of an independent cohort of IBD transcriptomes. Moreover, transcriptomes of IBD patients revealed a clear-cut clusterization of genes related with the maintenance of the inflammatory status. In conclusion, our results demonstrating that Vδ2 T cells have a proinflammatory profile in chronic IBD are suggestive of their participation in IBD and CAC pathogenesis.

In this paper we present a case of unexpected early local recurrence after surgery for colon cancer. Notably, an anastomotic recurrence was diagnosed two months after curative right hemicolectomy. Accurate preoperative endoscopic and radiological explorations were carried out, the resection was performed according to the oncological surgical principles, and the pathologic report confirmed the oncological radicality of the treatment performed. Therefore, the precocity of local recurrence appeared surprising, and led us to carry out a review of the literature in order to look into its possible explanations. The results of this research are presented.

Objectives This study sought to establish worldwide and regional diagnostic reference levels (DRLs) and achievable administered activities (AAAs) for single-photon emission computed tomography (SPECT) myocardial perfusion imaging (MPI). Background Reference levels serve as radiation dose benchmarks to compare individual laboratories against aggregated data, helping to identify sites in greatest need of dose reduction interventions. DRLs for SPECT MPI have previously been derived from national or regional registries. To date there have been no multiregional reports of DRLs for SPECT MPI from a single standardized dataset. Methods Data were submitted voluntarily to the INCAPS (International Atomic Energy Agency Nuclear Cardiology Protocols Study), a cross-sectional, multinational registry of MPI protocols. A total of 7,103 studies were included. DRLs and AAAs were calculated by protocol for each world region and for aggregated worldwide data. Results The aggregated worldwide DRLs for rest-stress or stress-rest studies employing technetium Tc 99m–labeled radiopharmaceuticals were 11.2 mCi (first dose) and 32.0 mCi (second dose) for 1-day protocols, and 23.0 mCi (first dose) and 24.0 mCi (second dose) for multiday protocols. Corresponding AAAs were 10.1 mCi (first dose) and 28.0 mCi (second dose) for 1-day protocols, and 17.8 mCi (first dose) and 18.7 mCi (second dose) for multiday protocols. For stress-only technetium Tc 99m studies, the worldwide DRL and AAA were 18.0 mCi and 12.5 mCi, respectively. Stress-first imaging was used in 26% to 92% of regional studies except in North America where it was used in just 7% of cases. Significant differences in DRLs and AAAs were observed between regions. Conclusions This study reports reference levels for SPECT MPI for each major world region from one of the largest international registries of clinical MPI studies. Regional DRLs may be useful in establishing or revising guidelines or simply comparing individual laboratory protocols to regional trends. Organizations should continue to focus on establishing standardized reporting methods to improve the validity and comparability of regional DRLs.

The tumor microenvironment supplies proinflammatory cytokines favoring a permissive milieu for cancer cell growth and invasive behavior. Here we show how breast cancer progression is facilitated by IL4 secreted by adipose tissue and estrogen receptor–positive and triple-negative breast cancer cell types. Blocking autocrine and paracrine IL4 signaling with the IL4Rα antagonist IL4DM compromised breast cancer cell proliferation, invasion, and tumor growth by downregulating MAPK pathway activity. IL4DM reduced numbers of CD44+/CD24− cancer stem-like cells and elevated expression of the dual specificity phosphatase DUSP4 by inhibiting NF-κB. Enforced expression of DUSP4 drove conversion of metastatic cells to nonmetastatic cells. Mechanistically, RNAi-mediated attenuation of DUSP4 activated the ERK and p38 MAPK pathways, increased stem-like properties, and spawned metastatic capacity. Targeting IL4 signaling sensitized breast cancer cells to anticancer therapy and strengthened immune responses by enhancing the number of IFNγ-positive CTLs. Our results showed the role of IL4 in promoting breast cancer aggressiveness and how its targeting may improve the efficacy of current therapies. Cancer Res; 77(12); 3268–79. ©2017 AACR.

Highlights • Total thyroidectomy is a safe and effective treatment for Graves’ disease. • It is associated with a very low incidence rate of post-operative complications. • Total thyroidectomy offers a rapid and definitive control of hyperthyroidism and its related symptoms., Purpose Thyroidectomy is the preferred approach as the definitive treatment for Graves’ disease. The outcomes for total thyroidectomy in a large series of 594 patients, who were observed in the last decade, will be presented in this study. Methods The study concerned a retrospective review of 594 patients, undergoing a total thyroidectomy for Graves’ disease. The incidence of complications and outcomes on hyperthyroidism and correlated symptoms resolution were also evaluated. Results The mean age of the patients was of 44.7 ± 12.7 years and 456 patients (76.7%) were females. The mean gland weight was 67.3 ± 10.8 g (range: 20–350 g) and, in 397 patients (66.8%), the gland weighed >40 g. The mean operative time was 125 ± 23.1 min (range: 65–212 min). Temporary and permanent hypocalcaemia developed in 241 (40.6%) and 3 patients (0.5%), respectively. Temporary and permanent recurrent laryngeal nerve palsy were recorded in 31 (5.2%) and 1 patients (0.16%) respectively. No patient developed a thyroid storm. On multivariate analysis, patient age ≤50 years (Odds ratio: 1; 95% Confidence Interval: 0.843–0.901) and thyroid weight >40 g (Odds ratio: 1; 95%, Confidence Interval: 0.852–0.974), were mainly associated with the occurrence of complications. Conclusion This high-volume surgeon experience demonstrates that total thyroidectomy is a safe and effective treatment for Graves’ disease. It is associated with a very low incidence rate of post-operative complications, most of which are transitory; therefore, it offers a rapid and definitive control of hyperthyroidism and its related symptoms.

Recently, immunotherapy has been shown to be an effective and helpful therapeutic option for the treatment of advanced non-small-cell lung cancer (NSCLC). The activity of antitumor T cells may be restored through the checkpoint blockade using anti-programmed death 1 or anti-programmed death ligand 1 (PD-L1) antibodies, showing, in several cancer patients, an increased progression-free survival and overall survival compared with classical chemotherapy. As recently shown by several studies, the PD-L1 expression levels in tumors may offer a selection criterion for patients to predict their immunotherapy response. In particular, NSCLC patients with high tumor PD-L1 levels (proportional score ≥ 50% for first-line therapy and ≥ 1% for second-line treatment, respectively) showed better response rates to immunotherapy and longer survival in first-line therapy compared with conventional chemotherapy. PD-L1, whose expression is evaluated by using immunohistochemistry analysis, is currently the only biomarker approved for clinical use in the first- and second-line monotherapy setting and therefore plays a central role in treatment decision-making for patients with advanced NSCLC. In this review we will discuss the key role of PD-L1 as a predictive biomarker of response to pembrolizumab therapy in NSCLC patients by describing the appropriate techniques and methodologies for immunohistochemical evaluation of PD-L1 expression and providing an overview of the clinical studies supporting its predictive significance.

Purpose To compare magnetic resonance imaging (MRI) findings with gadoxetic acid and gadobenate dimeglumine for the diagnosis of hepatic hemangiomas. Materials and Methods In this retrospective study, we included 26 hemangiomas (mean size was 14 mm ± 10 mm) in 19 patients (mean age 60 ± 14 years) scanned with both gadobenate dimeglumine MRI and gadoxetic acid MRI. For each patient, we collected multiple lesion variables including location, number, size and enhancement pattern on arterial, portal venous, 3-minute and hepatobiliary phases with both gadoxetic acid and gadobenate dimeglumine. The enhancement pattern with the two contrast agents was then compared. Results The typical enhancement pattern of hepatic hemangiomas was more common—though not statistically significant—with gadobenate dimeglumine compared to gadoxetic acid (57% [15 of 26] vs 42% [11 of 26], respectively; P = 0.4057 for both peripheral globular discontinuous enhancement in the arterial phase and centripetal fill-in in the portal venous phase). A significantly higher number of hemangiomas showed centripetal fill-in or hyperintensity in the 3-minute phase with gadobenate dimeglumine compared to gadoxetic acid (88% [23 of 26) vs 58% [15 of 26]; P = 0.0266). A pseudo washout sign in the 3-minute phase was detected in one of the 5 flash-filling hemangiomas with gadoxetic acid, but not gadobenate dimeglumine. All hemangiomas were hypointense in the hepatobiliary phase with both gadobenate dimeglumine and gadoxetic acid. Conclusions The enhancement pattern of hepatic hemangiomas may vary depending on the hepatobiliary agent, with more frequent lack of the typical pattern with gadoxetic acid compared to gadobenate dimeglumine.

Reconstruction after resection of advanced stage hidradenitis suppurativa is currently performed with pedicled perforator flaps, that allow functional reconstruction and preservation of shoulder function. Skin availability is limited by the possibility of closing the donor site primarily. Bilateral cases need to be treated in two stages, since the operation is carried out in the lateral decubitus. In this manuscript the application of bilateral and bipedicled DIEAP flaps to bilateral and extensive cases is presented.Between October 2008 and October 2018, 39 patients were treated for axillary hidradenitis suppurativa. Of these, 11 patients had bilateral reconstruction with bilateral DIEAP flaps (22 flaps) and one patient had unilateral reconstruction with a bipedicled DIEAP flap. 23 flaps were used. Twelve flaps were raised above Scarpa's fascia, 6 flaps werethinned after dissection. Three flaps were not thinned in the first stage. Average flap size was 14 × 17cm for the bilateral flaps, while the bipedicled flap was 15 × 32cm.Average operative time was 324 minutes. No flap necrosis was observed. Two patients had wound dehiscences in the axilla and one in the abdomen, all treated conservatively. One patient had a pyoderma gangrenosum at both surgical sites that healed after cortisone therapy. No revisions were needed for the flaps that were thinned during the primary operation. The three patients whose flaps where not thinned needed liposuction after three months for thinning. There was one disease recurrence, unilateral and treated surgically. Mean follow up was 64 months.Axillary reconstruction with the DIEAP flap allows reconstruction of large and bilateral defect in a single operation closing the donor site primarily. If the flap is thinned during the operation, no thinning seems to be needed postoperatively. Otherwise the flap shall be thinned by liposuction three months after the initial procedure. We believe that the benefits of this technique outweigh the added complexity of a microsurgical procedure when bilateral resections are needed, the defects are too wide to close the donor site of a pedicled flap primarily and the lower abdomen is free of disease.EINFüHRUNG: Die Rekonstruktion der Axilla nach Resektion bei fortgeschrittener Hidradenitis suppurativa (Akne inversa) erfolgt in unserer Erfahrung mit gestielten Perforans-Lappenplastiken, die eine funktionelle Rekonstruktion und einen Funktionserhalt der Schulter erlauben. Die Verfügbarkeit der Haut ist um die Axilla durch die Notwendigkeit eines primären Verschlusses der Entnahmestelle begrenzt. In dieser Arbeit werden die Anwendung und die Ergebnisse von bilateralen freien DIEP-Lappenplastiken bei Patienten mit bilateraler und großflächiger Resektion vorgestellt. Von Oktober 2008 bis Oktober 2018 wurden 39 Patienten mit Hidradenitis suppurativa chirurgisch behandelt. Bei 11 dieser Patienten erfolgte eine bilaterale Rekonstruktion mit bilateraler DIEP-Lappenplastik (22 Lappenplastiken). Bei einem Patienten wurde eine unilaterale Rekonstruktion mithilfe einer doppelt gestielten DIEP-Lappenplastik durchgeführt. Insgesamt wurden 23 Lappenpkastiken verwendet. Zwölf Lappenplastiken wurden über der Scarpa-Faszie gehoben, 6 Lappenplastiken wurden nach der Dissektion ausgedünnt. Drei Lappenplastiken wurden in der ersten Phase nicht ausgedünnt. Die durchschnittliche Lappengröße betrug bei den bilateralen Lappenplastiken 14 × 17 cm und beim doppelt gestielten Lappenplastiken 15 × 32 cm. Die mittlere Nachbeobachtungszeit lag bei 64 Monaten. Die durchschnittliche Operationsdauer lag bei 324 Minuten. Es wurden keine Lappennekrosen festgestellt. In zwei Fällen kam es zu einer axillären, in einem Fall zu einer abdominalen Wunddehiszenz. Diese wurden alle konservativ behandelt. Bei einem Patienten wurde an beiden Operationsstellen ein Pyoderma gangraenosum beobachtet, das nach Kortisontherapie abheilte. Bei den Lappenplastiken, die während des primären Eingriffs ausgedünnt wurden, war keine Revision erforderlich. Die drei Patienten mit den nicht ausgedünnten Lappen benötigten nach drei Monaten eine Liposuktion zur Ausdünnung. In einem Fall kam es zu einem Krankheitsrezidiv. Dieses war unilateral und wurde chirurgisch behandelt. Die Rekonstruktion der Axilla mit DIEP-Lappenplastiken ermöglicht die Rekonstruktion großer und bilateraler Defekte in einem einzigen Eingriff mit primärem Verschluss der Entnahmestelle. Wenn die Lappenplastik während der Operation ausgedünnt wird, scheint postoperativ keine weitere Ausdünnung erforderlich zu sein. Ansonsten sollte der Lappen drei Monate nach dem Ersteingriff durch Liposuktion ausgedünnt werden.

IgG4 autoantibodies in autoimmune myasthenia gravis are functionally monovalent, requiring a high-affinity threshold to reach pathogenic capacity. This capacity is dependent on self-antigen driven maturation, which includes the accumulation of indispensable somatic mutations that may alter electrostatic interactions with the antigen., Pathogenic muscle-specific tyrosine kinase (MuSK)–specific IgG4 autoantibodies in autoimmune myasthenia gravis (MG) are functionally monovalent as a result of Fab-arm exchange. The development of these unique autoantibodies is not well understood. We examined MG patient–derived monoclonal autoantibodies (mAbs), their corresponding germline-encoded unmutated common ancestors (UCAs), and monovalent antigen-binding fragments (Fabs) to investigate how affinity maturation contributes to binding and immunopathology. Mature mAbs, UCA mAbs, and mature monovalent Fabs bound to MuSK and demonstrated pathogenic capacity. However, monovalent UCA Fabs bound to MuSK but did not have measurable pathogenic capacity. Affinity of the UCA Fabs for MuSK was 100-fold lower than the subnanomolar affinity of the mature Fabs. Crystal structures of two Fabs revealed how mutations acquired during affinity maturation may contribute to increased MuSK-binding affinity. These findings indicate that the autoantigen drives autoimmunity in MuSK MG through the accumulation of somatic mutations such that monovalent IgG4 Fab-arm–exchanged autoantibodies reach a high-affinity threshold required for pathogenic capacity., Graphical Abstract

Objectives This study sought to describe worldwide variations in the use of myocardial perfusion imaging hardware, software, and imaging protocols and their impact on radiation effective dose (ED). Background Concerns about long-term effects of ionizing radiation have prompted efforts to identify strategies for dose optimization in myocardial perfusion scintigraphy. Studies have increasingly shown opportunities for dose reduction using newer technologies and optimized protocols. Methods Data were submitted voluntarily to the INCAPS (International Atomic Energy Agency Nuclear Cardiology Protocols Study) registry, a multinational, cross-sectional study comprising 7,911 imaging studies from 308 labs in 65 countries. The study compared regional use of camera technologies, advanced post-processing software, and protocol characteristics and analyzed the influence of each factor on ED. Results Cadmium-zinc-telluride and positron emission tomography (PET) cameras were used in 10% (regional range 0% to 26%) and 6% (regional range 0% to 17%) of studies worldwide. Attenuation correction was used in 26% of cases (range 10% to 57%), and advanced post-processing software was used in 38% of cases (range 26% to 64%). Stress-first single-photon emission computed tomography (SPECT) imaging comprised nearly 20% of cases from all world regions, except North America, where it was used in just 7% of cases. Factors associated with lower ED and odds ratio for achieving radiation dose ≤9 mSv included use of cadmium-zinc-telluride, PET, advanced post-processing software, and stress- or rest-only imaging. Overall, 39% of all studies (97% PET and 35% SPECT) were ≤9 mSv, while just 6% of all studies (32% PET and 4% SPECT) achieved a dose ≤3 mSv. Conclusions Newer-technology cameras, advanced software, and stress-only protocols were associated with reduced ED, but worldwide adoption of these practices was generally low and varied significantly between regions. The implementation of dose-optimizing technologies and protocols offers an opportunity to reduce patient radiation exposure across all world regions.

Pathogenic IgG4 autoantibodies in autoimmune myasthenia gravis (MG) are functionally monovalent as a result of Fab-arm exchange. The origin and development of these unique autoantibodies are not well understood. We examined MG patient-derived monoclonal autoantibodies (mAbs), their corresponding germline-encoded unmutated common ancestors (UCA) and monovalent antigen-binding fragments (Fabs) to investigate how antigen-driven affinity maturation contributes to both binding and immunopathology. Mature mAbs, their UCA counterparts and mature monovalent Fabs bound to the autoantigen and retained their pathogenic capacity. However, monovalent UCA Fabs still bound the autoantigen but lost their pathogenic capacity. The mature Fabs were characterized by very high affinity (sub-nanomolar) driven by a rapid on-rate and slow off-rate. However, the UCA affinity was approximately 100-fold less than that of the mature Fabs, which was driven by a rapid off-rate. Crystal structures of two Fabs shed light on how mutations acquired during affinity maturation may contribute to increased MuSK binding affinity. These collective findings indicate that the autoantigen initiates the autoimmune response in MuSK MG and drives autoimmunity through the accumulation of somatic hypermutation such that monovalent IgG4 Fab-arm exchanged MG autoantibodies reach a high affinity threshold required for pathogenic capacity.SummaryIgG4 autoantibodies in autoimmune myasthenia gravis are functionally monovalent, requiring a high affinity threshold featuring fast on/slow off rates, to reach pathogenic capacity. This capacity is dependent on self-antigen initiated and driven maturation, which includes the accumulation of indispensable somatic hypermutations that may alter electrostatic interactions with the antigen.

At very low diffusion weighting the diffusion MRI signal is affected by intravoxel incoherent motion (IVIM) caused by dephasing of magnetization due to incoherent blood flow in capillaries or other sources of microcirculation. While IVIM measurements at low diffusion weightings have been frequently used to investigate perfusion in the body as well as in malignant tissue, the effect and origin of IVIM in normal brain tissue is not completely established. We investigated the IVIM effect on the brain diffusion MRI signal in a cohort of 137 radiologically-normal patients (62 male; mean age = 50.2 ± 17.8, range = 18 to 94). We compared the diffusion tensor parameters estimated from a mono-exponential fit at b = 0 and 1000 s/mm2 versus at b = 250 and 1000 s/mm2. The asymptotic fitting method allowed for quantitative assessment of the IVIM signal fraction f* in specific brain tissue and regions. Our results show a mean (median) percent difference in the mean diffusivity of about 4.5 (4.9)% in white matter (WM), about 7.8 (8.7)% in cortical gray matter (GM), and 4.3 (4.2)% in thalamus. Corresponding perfusion fraction f* was estimated to be 0.033 (0.032) in WM, 0.066 (0.065) in cortical GM, and 0.033 (0.030) in the thalamus. The effect of f* with respect to age was found to be significant in cortical GM (Pearson correlation ρ ​= ​0.35, p ​= ​3*10−5) and the thalamus (Pearson correlation ρ = 0.20, p = 0.022) with an average increase in f* of 5.17*10−4/year and 3.61*10−4/year, respectively. Significant correlations between f* and age were not observed for WM, and corollary analysis revealed no effect of gender on f*. Possible origins of the IVIM effect in normal brain tissue are discussed.

There is growing concern about radiation exposure from nuclear myocardial perfusion imaging (MPI), particularly among younger patients who are more prone to develop untoward effects of ionizing radiation, and hence US and European professional society guidelines recommend age as a consideration in weighing radiation risk from MPI. We aimed to determine how patient radiation doses from MPI vary across age groups in a large contemporary international cohort.Data were collected as part of a global cross-sectional study of centers performing MPI coordinated by the International Atomic Energy Agency (IAEA). Sites provided information on each MPI study completed during a single week in March-April 2013. We compared across age groups laboratory adherence to pre-specified radiation-related best practices, radiation effective dose (ED; a whole-body measure reflecting the amount of radiation to each organ and its relative sensitivity to radiation's deleterious effects), and the proportion of patients with ED ≤ 9 mSv, a target level specified in guidelines.Among 7911 patients undergoing MPI in 308 laboratories in 65 countries, mean ED was 10.0 ± 4.5 mSv with slightly higher exposure among younger age groups (trend p value 0.001). There was no difference in the proportion of patients with ED ≤ 9 mSv across age groups, or in adherence to best practices based on the median age of patients in a laboratory.In contemporary nuclear cardiology practice, the age of the patient appears not to impact protocol selection and radiation dose, contrary to professional society guidelines.

Background and objectives The Axillary Lymph Node Dissection (ALND) is the standard treatment in patients with invasive breast cancer and sentinel node metastasis, but in 60% of the cases there is no further axillary neoplastic involvement, so this invasive intervention represents an overtreatment. The purpose of the study is to identify patients with low risk of additional nodal metastases, to omit ALND. Methods The MSKCC Additional nodal metastasis nomogram was applied on a sample of 175 patients with invasive breast cancer who underwent ALND after detection of macrometastasis with the extemporaneous examination of the sentinel lymph node. Patients were classified as "low risk" when the result of the nomogram was ≤50%. Sensitivity, specificity, positive and negative predictive values and AUC (Area Under Curve) of the ROC curve of the nomogram were then calculated. Results A cut-off by 50% yielded 92.3% sensitivity, 81,4% specificity, 80% positive predictive value and 92.9% negative predictive value. The ROC curve AUC in these patients was 0.885. Conclusions The MSKCC nomogram has proven to be an effective tool in estimating the axillary lymph node status and it can potentially be used to better select the patients with sentinel node macrometastasis who can actually benefit from ALND.

Dietary restrictions, including fasting (or long-term starvation), calorie restriction (CR), and short-term starvation (STS), are considered a strong rationale that may protect against various diseases, including age-related diseases and cancer. Among dietary approaches, STS, in which food is not consumed during designed fasting periods but is typically not restricted during designated feeding periods, seems to be more suitable, because other dietary regimens involving prolonged fasting periods could worsen the health conditions of cancer patients, being they already naturally prone to weight loss. Until now, the limited amount of available data does not point to a single gene, pathway, or molecular mechanism underlying the benefits to the different dietary approaches. It is well known that the healthy effect is mediated in part by the reduction of nutrient-related pathways. The calorie restriction and starvation (long- and short-term) also suppress the inflammatory response reducing the expression, for example, of IL-10 and TNF-α, mitigating pro-inflammatory gene expression and increasing anti-inflammatory gene expression. The dietary restriction may regulate both genes involved in cellular proliferation and factors associated to apoptosis in normal and cancer cells. Finally, dietary restriction is an important tool that may influence the response to chemotherapy in preclinical models. However, further data are needed to correlate dietary approaches with chemotherapeutic treatments in human models. The aim of this review is to discuss the effects of various dietary approaches on the cancer progression and therapy response, mainly in preclinical models, describing some signaling pathways involved in these processes.

Purpose: Intraoperative neuromonitoring (IONM) of the recurrent laryngeal nerve (RLN) is a useful technique that can be applied to assess the nerve functionality at the end of the first side lobectomy in a planned total resection to prevent the bilateral injury of the RLN. Here we describe the process of informed consent of patients, who were subjected to a 2-stage thyroidectomy, and its effect on the patients' willingness to be operated on as well as their consent rates. Methods: A retrospective observational study of patients, undergoing thyroidectomy with standardized IONM, was conducted from January 2019 to December 2019. All patients were preoperatively informed about the possibility of undergoing a 2-stage thyroidectomy. The outcome of this information was evaluated through a specific questionnaire that the patients were asked to fill in. Results: Eighty patients were initially included in the analysis. The treatment was discontinued in 8 patients, who were originally eligible to total thyroidectomy, due to the detection of a loss of signal in the electromyography. The analysis of the results of the questionnaires highlighted a high compliance of the patients with the expectation of a possible new intervention. Conclusion: Two-stage thyroidectomy proved to be a reliable surgical approach and appeared to be largely accepted by the patients.

The purpose of this study was to edit a renovated thyroidectomy difficulty scale (rTDS) in order to identify underlying thyroid diseases with a longer operative time and higher technical difficulty, also considering preservation of recurrent laryngeal nerve. We developed a renovated scale with a maximum score of 20 points by creating a form in which five variables were considered: vascularity, friability, mobility/fibrosis, gland size and difficulty in preservation of the recurrent laryngeal nerve. Two surgeons separately evaluated each of these. Through a simple linear regression analysis, we have analyzed the relationship between rTDS score and operative times, and between rTDS score and preservation of recurrent nerve. Eventually, Spearman’s rank correlation coefficient has been used in order to evaluate our double-blind study. Our cohort included 131 patients undergoing total thyroidectomy. The mean of the rTDS was 9.00 ± 3.67 for Surgeon A and 8.31 ± 3.42 for Surgeon B, with Spearman’s rank correlation coefficient between surgeons of 0.85 (p < 0.0001). We have shown that the rTDS score significantly influences the operating times (R2 = 0.44 for surgeon A, R2 = 0.46 for B, p < 0.0001 for both). Moreover, we can say that the rTDS score significantly influences preservation of the recurrent nerve (R2 = 0.37, Beta 0.61, 8.84 t test, p < 0.0001). Our rTDS is a useful tool and, thanks to it, we identified hyperthyroidism and goiter as the hardest underlying disease for surgery. Thus our scale could change operative approach, resulting in better surgeries’ scheduling and identification of pathologies that require higher attention.

The purpose of this study is to verify whether the performance of ultrasound-guided quadrantectomy (USGQ) versus palpation-guided quadrantectomy (PGQ) can reduce the incidence of positive margins and if it can change the attitude of the surgeon. A retrospective study was conducted on 842 patients underwent quadrantectomy for breast cancer, 332 of them underwent USGQ, whereas 550 underwent PGQ. The histological type of the tumors and the margin status obtained with the histological examination were compared. The histological examination of the surgical specimen showed involvement of the margins in 24/842 patients (2.85%), 22 (2.61%) of them belonged to the PGQ group, and two to the USGQ group (P = 0.0011). The highest rate of microscopically positive margins was, statistically significant, for carcinoma in situ, when compared with patients with invasive carcinoma (0.0001). USGQ technique showed several advantages compared with PGQ. In fact, the former notes a lower positive margin rate and, consequently, a lower rate of reintervention. In addition, it may change the surgeon's attitude by causing him to remove another slice of margin to ensure more histological negativity. It should be the gold standard technique for breast-conservative surgery of palpable tumors.

OBJECTIVE While nuclear myocardial perfusion imaging (MPI) offers many benefits to patients with known or suspected cardiovascular disease, concerns exist regarding radiation-associated health effects. Little is known regarding MPI practice in Africa. We sought to characterise radiation doses and the use of MPI best practices that could minimise radiation in African nuclear cardiology laboratories, and compare these to practice worldwide. METHODS Demographics and clinical characteristics were collected for a consecutive sample of 348 patients from 12 laboratories in six African countries over a one-week period from March to April 2013. Radiation effective dose (ED) was estimated for each patient. A quality index (QI) enumerating adherence to eight best practices, identified a priori by an IAEA expert panel, was calculated for each laboratory. We compared these metrics with those from 7 563 patients from 296 laboratories outside Africa. RESULTS Median (interquartile range) patient ED in Africa was similar to that of the rest of the world [9.1 (5.1-15.6) vs 10.3 mSv (6.8-12.6), p = 0.14], although a larger proportion of African patients received a low ED, ≤ 9 mSv targeted in societal recommendations (49.7 vs 38.2%, p < 0.001). Bestpractice adherence was higher among African laboratories (QI score: 6.3 ± 1.2 vs 5.4 ± 1.3, p = 0.013). However, median ED varied significantly among African laboratories (range: 2.0-16.3 mSv; p < 0.0001) and QI range was 4-8. CONCLUSION Patient radiation dose from MPI in Africa was similar to that in the rest of the world, and adherence to best practices was relatively high in African laboratories. Nevertheless there remain opportunities to further reduce radiation exposure to African patients from MPI.

γδ T cells usually infiltrate many different types of cancer, but it is unclear whether they inhibit or promote tumor progression. Moreover, properties of tumor-infiltrating γδ T cells and those in the corresponding normal tissue remain largely unknown. Here we have studied features of γδ T cells in colorectal cancer, normal colon tissue and peripheral blood, and correlated their levels with clinicopathologic hallmarks. Flow cytometry and transcriptome analyses showed that the tumor comprised a highly variable rate of TILs (5–90%) and 4% γδ T cells on average, with the majority expressing Vδ1. Most Vδ1 and Vδ2 T cells showed a predominant effector memory phenotype and had reduced production of IFN- γ which was likely due to yet unidentified inhibitory molecules present in cancer stem cell secretome. Transcriptome analyses revealed that patients containing abundant γδ T cells had significantly longer 5-year disease free survival rate, suggesting their efficacy in controlling tumor at very early stage.

Objectives The aim of this study was to investigate gender-based differences in nuclear cardiology practice globally, with a particular focus on laboratory volume, radiation dose, protocols, and best practices. Background It is unclear whether gender-based differences exist in radiation exposure for nuclear cardiology procedures. Methods In a large, multicenter, observational, cross-sectional study encompassing 7,911 patients in 65 countries, radiation effective dose was estimated for each examination. Patient-level best practices relating to radiation exposure were compared between genders. Analysis of covariance was used to determine any difference in radiation exposure according to gender, region, and the interaction between gender and region. Linear, logistic, and hierarchical regression models were developed to evaluate gender-based differences in radiation exposure and laboratory adherence to best practices. The study also included the United Nations Gender Inequality Index and Human Development Index as covariates in multivariable models. Results The proportion of myocardial perfusion imaging studies performed in women varied among countries; however, there was no significant correlation with the Gender Inequality Index. Globally, mean effective dose for nuclear cardiology procedures was only slightly lower in women (9.6 ± 4.5 mSv) than in men (10.3 ± 4.5 mSv; p Conclusions Despite significant worldwide variation in best practice use and radiation doses from nuclear cardiology procedures, only small differences were observed between genders worldwide. Regional variations noted in myocardial perfusion imaging use and radiation dose offer potential opportunities to address gender-related differences in delivery of nuclear cardiology care.

Clostridium botulinum neurotoxins (BoNTs) released by the bacterium Clostridium botulinum are the most potent toxins causing the fatal disease called botulism. There are seven distinct serotypes of BoNTs (A to G) released by various strains of botulinum. They all have high sequence homology and similar three-dimensional structure. The toxicity of BoNT follows a four-step process–binding, internalization, translocation, and cleavage of its target protein, one of the three components of the SNARE complex (Soluble N-ethylmaleimde-sensitive factor attachment protein receptor) required for membrane docking and neurotransmitter release. Cleavage of one of the three proteins causes blockage of neurotransmitter release leading to flaccid paralysis. Though anyone of the above four steps could be a target for developing antidotes for botulism, the catalytic domain is the most suitable target for post exposure treatment. Of the seven serotypes BoNT/A, B, E and probably F affect humans, with BoNT/A considered to be the most potent. Development of drugs for botulism is focused on serotype specific inhibitors, but pan-active inhibitor acting on several serotypes is preferable since it is difficult to identify the serotype before the treatment, especially since there is at least a 36 h window before botulism can be diagnosed. Using structure-based drug discovery, we have developed three heptapeptides based on the SNARE proteins which inhibit BoNT/A, B and E equally well. Probable reasons for pan-activity of these peptides are discussed.

BACKGROUND: Although Ki-ras and TP53 mutations have probably been the genetic abnormalities most exhaustively implicated and studied in colorectal cancer (CRC) progression, their significance in terms of disease relapse and overall survival has not yet clearly been established. PATIENTS AND METHODS: A prospective study was carried out on paired tumor and normal colon tissue samples from a consecutive series of 160 previously-untreated patients, undergoing resective surgery for primary operable sporadic CRC. Mutations within the TP53 (exons 5-8) and Ki-ras (exon 2) genes were detected by PCR-SSCP analyses following sequencing. RESULTS: Mutation analyses of exons 5 to 8 of the TP53 gene showed mutations in 43% (68/160) of the cases, while mutation analyses of exon 2 of the Ki-ras gene showed mutations in 46% (74/160) of the cases. Multivariate analyses showed that clinical outcome were strongly associated with the presence of specific TP53 mutations in L3 domain alone (only in DFS) or in combination with specific Ki-ras mutations at codon 13. CONCLUSION: Specific TP53 mutations in L3 domain alone (only in DFS) or in combination with specific Ki-ras mutations at codon 13 are associated with a worse prognosis in sporadic CRC.

P63 is a transcription factor belonging to the family of p53, essential for the development and differentiation of epithelia. In recent years, it has become clear that altered expression of the different isoforms of this gene can play an important role in carcinogenesis. The p63 gene encodes for two main isoforms known as TA and ΔN p63 with different functions. The role of these different isoforms in sustaining tumor progression and metastatic spreading however has not entirely been clarified. Here we show that breast cancer initiating cells express ΔNp63 isoform that supports a more mesenchymal phenotype associated with a higher tumorigenic and metastatic potential. On the contrary, the majority of cells within the tumor appears to express predominantly TAp63 isoform. While ΔNp63 exerts its effects by regulating a PI3K/CD44v6 pathway, TAp63 modulates this pathway in an opposite fashion. As a result, tumorigenicity and invasive capacity of breast cancer cells is a balance of the two isoforms. Finally, we found that tumor microenvironmental cytokines significantly contribute to the establishment of breast cancer cell phenotype by positively regulating ΔNp63 and CD44v6 expression.

BACKGROUND This paper examines the current status of radiation exposure to patients in myocardial perfusion imaging (MPI) in Asia.Methods and Results:Laboratories voluntarily provided information on MPI performed over a 1-week period. Eight best practice criteria regarding MPI were predefined by an expert panel. Implementation of ≥6 best practices (quality index [QI] ≥6) was pre-specified as a desirable goal for keeping radiation exposure at a low level. Radiation effective dose (ED) in 1,469 patients and QI of 69 laboratories in Asia were compared against data from 239 laboratories in the rest of the world (RoW). Mean ED was significantly higher in Asia (11.4 vs. 9.6 mSv; P

Background There is concern about radiation exposure with radionuclide myocardial perfusion imaging (MPI). This sub-study of the International Atomic Energy Agency (IAEA) Nuclear Cardiology Protocols Study reports radiation doses from MPI, and use of dose-optimisation protocols in Australia and New Zealand (ANZ), and compares them with data from the rest of the world. Methods Data were collected from 7911 MPI studies performed in 308 laboratories worldwide in one week in 2013, including 439 MPI studies from 34 ANZ laboratories. For each laboratory, effective radiation dose (ED) and a quality index (QI) score (out of 8) based on pre-specified "best practices'' was determined. Results In ANZ patients, ED ranged from 0.9-17.9 milliSievert (mSv). Median ED was similar in ANZ compared with the rest of the world (10.0 (IQR: 6.5-11.7) vs. 10.0 (IQR 6.4-12.6, P=0.15), as were mean QI scores (5.5 +/- 0.7 vs. 5.4 +/- 1.3, P= 0.84). Use of stress-only imaging (17.6% vs. 31.8% of labs, P= 0.09) and weight-based dosing of technetium-99m (14.7% vs. 30.3%, P= 0.07) was lower in ANZ compared with the rest of the world but this difference was not statistically significant. Median ED was significantly lower in metropolitan versus nonmetropolitan laboratories (10.1 mSv vs. 11.6 mSv, P < 0.01), although mean QI scores were similar (5.4 +/- 0.8 vs. 5.5 +/- 0.7, P= 0.75). Conclusion Across ANZ, there is variability in ED from MPI, and use of radiation safety practices, particularly between metropolitan and non-metropolitan laboratories. Overall, ANZ laboratories have a similar median ED to laboratories in the rest of the world.

Summary Over the last few years, there has been an enormous increase in the use of needle core biopsy (CB) for the histopathological characterisation of suspect lesions of the breast. The aim of this study was to verify the diagnostic reliability of CB by comparing the histological results obtained with the use of this technique with those obtained from the whole of the surgically resected specimen. We studied 198 out of 426 patients with clinically and/or radiologically suspect breast lesions. We found correspondence between the histological examination of the whole of the excised specimen and that of the CB in 94.9% of the cases of infiltrating carcinoma and in 71.4% of those involving ductal carcinomas in situ. The predictive value of CB was 98.9%, sensitivity was 96.1% and specificity 93.3%. These results confirmed that CB is an extremely reliable diagnostic tool in the definition of breast lesions.

Several studies report a higher rate of papillary thyroid carcinomas (PTC) in patients with Hashimoto thyroiditis (HT), indicating a possible correlation between the two diseases. We studied a group of 89 subjects undergoing surgery for thyroid carcinomas compared with a control group of 89 subjects operated on for normofunctioning goiter, and a second group of 47 patients undergoing total thyroidectomy for HT. Association with HT was found in 19 of the 71 PTC subjects (26.7%) and in 8 goiter patients (8.9%), which was a significant difference ( P < 0.02). Thirteen of the HT patients, mostly with the nodular form, showed coexistent PTC (27.6%). HT and PTC coexisted in several morphological, immunohistochemical, and biomolecular aspects; increased incidence of PTC in HT patients might therefore indicate that HT is a precursor of thyroid cancer. Further studies are required, however, in order to confirm this hypothesis; until then, HT patients should undergo careful clinical and technical follow-up.

Some studies have shown a direct relationship between nutritional status and survival in Cystic Fibrosis (CF) patients. Body wasting, defined as a percentage of the ideal body weight for age, has been shown to be an independent predictor of mortality in CF. With respect to height only two studies were performed and these studies suggested that stunting is an important determinant of survival but both did not adjust statistical analysis for confounding variables. We aimed at determining the association between stunting and risk of mortality in CF patients.393 CF patients older than 6 years of age, 95 deceased, as cases, and 298 live, as controls, were enrolled in a nested case-control study. Stunting was defined by a height percentile5th. We performed a multivariate statistical analysis including height percentile and the following possible confounding variables: age, gender, Body Mass Index (BMI), Forced Expiratory Volume in 1 s (FEV1), genotype, pancreatic status, CF-related diabetes, colonization with Pseudomonas aeruginosa and/or Burkholderia cepacia.In the adjusted analyses stunting (OR 2.22 [IC 95%1.10-4.46]), wasting (OR 5.27 [IC 95% 2.66-10.41]), and FEV1 40% of predicted (OR 10.60 [IC 95% 5.43-20.67]) resulted the covariates that significantly predict the risk of mortality.Our study shows, for the first time, that stunting is a significant and independent risk factor for mortality in CF patients, and warrants an intervention of nutritional rehabilitation. Considering that nutritional interventions in stunted patients should be prolonged, are invasive and expensive, and might affect self-esteem and body image, their efficacy should be fully assessed by Randomised Controlled Trials.

Background/Aims: We evaluated the diagnostic variability and reproducibility of endoscopic signs in two populations with a different pretest likelihood of celiac disease (CD). Methods: We recruited 289 CD patients (both adults and children) in a multicenter prospective study. Group 1 (high risk) included 111 patients referred for positive serology. Group 2 (low risk) included 178 unselected patients. Mosaic pattern, reduction/loss of Kerckring's folds, scalloping of the valvulae conniventes and a nodular pattern were the endoscopic findings looked for in the duodenum. Results: In group 1, the sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of endoscopic findings were 100, 84.6, 94.2 and 100% in adults, and 86.8, 9.1, 82.1 and 12.5% in children. In group 2, the sensitivity, specificity, PPV and NPV of endoscopic findings were 33.3, 91.4, 7.7 and 98.5% in adults, and noncalculable, 78.3, 0.0 and 100% in children. Comparing group 1 and group 2, there was a statistically significant difference in sensitivity and PPV in adults, and in specificity, PPV and NPV in children. Concerning the reproducibility of endoscopic findings, a wide variability of κ values was found. Conclusion: Endoscopic signs have low reproducibility for CD, and their diagnostic value in selecting patients for multiple intestinal biopsies is unacceptable, especially in populations with low disease prevalence.

Group Information: The INCAPS Investigators Group includes executive committee members A. J. Einstein (chair), T. N. B. Pascual (IAEA project lead), D. Paez (IAEA section head), M. Dondi (IAEA section head); N. Better, S.E. Bouyoucef, G. Karthikeyan, R. Kashyap, V. Lele, F. Mut, V. P. C. Magboo, J. J. Mahmarian, M. Mercuri, M. M. Rehani, and J. V. Vitola, and regional coordinators E. Alexanderson (Latin America), A. Allam (Africa andMiddle East), M. H. Al-Mallah (Middle East), N. Better (Oceania), S. E. Bouyoucef (Africa), H. Bom (East Asia), A. Flotats (Europe), S. Jerome (United States), P. A. Kaufmann (Europe), V. Lele (South Asia), O. Luxenburg (Israel), J. Mahmarian (North America), L. J. Shaw (North America), S. R. Underwood (United Kingdom), and J. Vitola (Latin America). Members by region include W. Amouri, H. Essabbah, S. S. Gassama, K. B. Makhdomi, G. I. E. El Mustapha, N. El Ouchdi, N. Qais, N. Soni, andW. Vangu (Africa); R. M. Abazid, B. Adams, V. Agarwal, M. A. Alfeeli, N. Alnafisi, L. Bernabe, G. G. Bural, T. Chaiwatanarat, J. M. Chandraguptha, G. J. Cheon, I. Cho, A. S. Dogan, M. Eftekhari, A. Frenkel, I. Garty, S. George, P. Geramifar, H. Golan, S. Habib, R. Hussain, H. Im, H-J. Jeon, T. Kalawat, W. J. Kang, F. Keng, A. Klaipetch, P. G. Kumar, J. Lee, W.W. Lee, I. Lim, C. M. M. Macaisa, G. Malhotra, B. R. Mittal, M. H. Mohammad, P. Mohan, I. D. Mulyanto, D. Nariman, U. N. Nayak, K. Niaz, G. Nikolov, J. M. Obaldo, E. Ozturk, J. M. Park, S. Park, C. D. Patel, H. K. Phuong, A. P. Quinon, T. R. Rajini, Y. Saengsuda, J. Santiago, H. B. Sayman, A. S. Shinto, V. Sivasubramaniyan, M. H. Son, P. Sudhakar, G. M. S. Syed, N. Tamaki, K. Thamnirat, T. Thientunyakit, S. Thongmak, D. N. Velasco, A. Verma, U. Vutrapongwatana, Y. Wang, K. S. Won, Z. Yao, T. Yingsa-nga, R. Yudistiro, K. T. Yue, and N. Zafrir (Asia); S. C. Adrian, D. Agostini, S. Aguade, G. Armitage, M. Backlund, M. Backman, M. Baker, M. T. Balducci, C. Bavelaar, M. Berovic, F. Bertagna, R. Beuchel, A. Biggi, G. Bisi, R. Bonini, A. Bradley, L. Brudin, I. Bruno, E. Busnardo, R. Casoni, A. Choudhri, C. Cittanti, R. Clauss, D. C. Costa, M. Costa, K. Dixon, M. Dziuk, N. Egelic, I. Eriksson, G. Fagioli, D. B. de Faria, L. Florimonte, A. Francini, M. French, E. Gallagher, I. Garai, O. Geatti, D. Genovesi, L. Gianolli, A. Gimelli, E. del Giudice, S. Halliwell, M. J. Hansson, C. Harrison, F. Homans, F. Horton, D. Jedrzejuk, J. Jogi, A. Johansen, H. Johansson, M. Kalnina, M. Kaminek, A. Kiss, M. Kobylecka, M. Kostkiewicz, J. Kropp, R. Kullenberg, T. Lahoutte, O. Lang, Y. H. Larsson, M. Lazar, L. Leccisotti, N. Leners, O. Lindner, R. W. Lipp, A. Maenhout, L. Maffioli, C. Marcassa, B. Martins, P. Marzullo, G. Medolago, J. B. Meeks, C. G. Mendiguchia, S. Mirzaei, M. Mori, B. Nardi, S. Nazarenko, K. Nikoletic, R. Oleksa, T. Parviainen, J. Patrina, R. Peace, C. Pirich, H. Piwowarska-Bilska, S. Popa, V. Prakash, V. Pubul, L. Puklavec, S. Rac, M. Ratniece, S. A. Rogan, A. Romeo, M. Rossi, D. Ruiz, N. Sabharwal, B. G. Salobir, A. I. Santos, S. Saranovic, A. Sarkozi, R. P. Schneider, R. Sciagra, S. Scotti, Z. Servini, L. R. Setti, S.-A. Starck, D. Vajauskas, J. Veselý, A. Vieni, A. Vignati, I. M. Vito, K. Weiss, D. Wild, andM. Zdraveska-Kochovska (Europe); R. N. Aguro, N. Alvarado, C. M. Barral, M. Beretta, I. Berrocal, J. F. Batista Cuellar, T.-M. Cabral Chang, L. O. Cabrera Rodriguez, J. Canessa, G. Castro Mora, A. C. Claudia, G. F. Clavelo, A. F. Cruz Jr, F. F. Faccio, K. M. Fernandez, J. R. Gomez Garibo, U. Gonzalez, P. Gonzalez, M. A. Guzzo, J. Jofre, M. Kapitan, G. Kempfer, J. L. Lopez, T. Massardo, I. Medeiros Colaco, C. T. Mesquita, M. Montecinos, S. Neubauer, L. M. Pabon, A. Puente, L. M. Rochela Vazquez, J. A. Serna Macias, A. G. Silva Pino, F. Z. Tartari Huber, A. P. Tovar, L. Vargas, and C. Wiefels (Latin America); A. Aljizeeri, R. J. Alvarez, D. Barger, W. Beardwood, J. Behrens, L. Brann, D. Brown, H. Carr, K. Churchwell, G. A. Comingore, J. Corbett, M. Costello, F. Cruz, T. Depinet, S. Dorbala, M. Earles, F. P. Esteves, E. Etherton, R. J. Fanning Jr, J. Fornace, L. Franks, H. Gewirtz, K. Gulanchyn, C.-L. Hannah, J. Hays, J. Hendrickson, J. Hester, K. Holmes, S. Jerome, A. Johnson, C. Jopek, H. Lewin, J. Lyons, C. Manley, J. Meden, S. Moore, W. H. Moore, V. Murthy, R. Nace, D. Neely, L. Nelson, O. Niedermaier, D. Rice, R. Rigs, K. Schiffer, E. Schockling, T. Schultz, T. Schumacker, B. Sheesley, A. Sheikh, B. Siegel, A. M. Slim, J. Smith, M. Szulc, N. Tanskersley, P. Tilkemeier, G. D. Valdez, R. Vrooman, D. Wawrowicz, and D. E. Winchester (North America); and A. Alcheikh, B. Allen, E. Atkins, J. Bevan, C. Bonomini, J. Christiansen, L. Clack, E. Craig, H. Dixson, I. Duncan, S. Fredericks, S. Gales, R. Hampson, T. Hanley, K. Hartcher, J. Hassall, B. Kelley, S. Kelly, T. Kidd, T. de Kort, G. Larcos, W. Macdonald, C. McGrath, E. Murdoch, S. O’Malley, M. O’Rourke, M. Pack, R. Pearce, R. Praehofer, S. Ramsay, L. Scarlett, K. Smidt, F. Souvannavong, K. Taubman, G. Taylor, K. Tse, S. Unger, and J. Weale (Oceania).

Purpose Nuclear cardiology is widely used to diagnose coronary artery disease and to guide patient management, but data on current practices, radiation dose-related best practices, and radiation doses are scarce. To address these issues, the IAEA conducted a worldwide study of nuclear cardiology practice. We present the European subanalysis. Methods In March 2013, the IAEA invited laboratories across the world to document all SPECT and PET studies performed in one week. The data included age, gender, weight, radiopharmaceuticals, injected activities, camera type, positioning, hardware and software. Radiation effective dose was calculated for each patient. A quality score was defined for each laboratory as the number followed of eight predefined best practices with a bearing on radiation exposure (range of quality score 0 - 8). The participating European countries were assigned to regions (North, East, South, and West). Comparisons were performed between the four European regions and between Europe and the rest-of-the-world (RoW). Results Data on 2,381 European patients undergoing nuclear cardiology procedures in 102 laboratories in 27 countries were collected. A cardiac SPECT study was performed in 97.9 % of the patients, and a PET study in 2.1 %. The average effective dose of SPECT was 8.0 +/- 3.4 mSv (RoW 11.4 +/- 4.3 mSv; P < 0.001) and of PET was 2.6 +/- 1.5 mSv (RoW 3.8 +/- 2.5 mSv; P < 0.001). The mean effective doses of SPECT and PET differed between European regions (P < 0.001 and P = 0.002, respectively). The mean quality score was 6.2 +/- 1.2, which was higher than the RoW score (5.0 +/- 1.1; P < 0.001). Adherence to best practices did not differ significantly among the European regions (range 6 to 6.4; P = 0.73). Of the best practices, stress-only imaging and weight-adjusted dosing were the least commonly used. Conclusion In Europe, the mean effective dose from nuclear cardiology is lower and the average quality score is higher than in the RoW. There is regional variation in effective dose in relation to the best practice quality score. A possible reason for the differences between Europe and the RoW could be the safety culture fostered by actions under the Euratom directives and the implementation of diagnostic reference levels. Stress-only imaging and weight-adjusted activity might be targets for optimization of European nuclear cardiology practice.

Aliment Pharmacol Ther 2011; 33: 697–706 Summary Background Accuracy of intraepithelial lymphocytes counts for diagnosing mild enteropathy coeliac disease in absence of villous atrophy can be limited by inappropriate controls included in the studies. Aim To determine the diagnostic accuracy of intraepithelial lymphocytes counts utilising controls lacking HLA coeliac disease-associated alleles. Methods Intraepithelial lymphocytes counting at villus tip and per 100 enterocytes was performed at haematoxylin and eosin (H&E) and CD3-stainings in: 29 cases (21 with potential coeliac disease and 8 affected by latent coeliac disease) representing the patient population and 14 noncoeliac controls lacking HLA-DQ2/DQ8 alleles. Results Threshold (mean + 2 s.d.) of duodenal intraepithelial lymphocytes at villus tip and per 100 enterocytes in noncoeliac controls was respectively: 3.5 and 18 at H&E, 3.2 and 17 following CD3-staining. Considering the whole patient population, the sensitivity of tip intraepithelial lymphocytes in detecting mild enteropathy coeliac disease was 90% (95% CI = 72.6–97.8) both at H&E and CD3-stainings. The sensitivity of intraepithelial lymphocytes per 100 enterocytes was 93% (95% CI = 77.2–99.2) both at H&E and CD3-staining. Specificity of both intraepithelial lymphocytes counts was 100% (95% CI = 76.8–100). Using a threshold of 25 intraepithelial lymphocytes per 100 enterocytes could miss 59% of cases at H&E and 48% following CD3-staining. Conclusions Intraepithelial lymphocytes counts are diagnostic feasible tools to detect mild enteropathy coeliac disease. Threshold of duodenal intraepithelial lymphocytes may be lower than currently accepted.

The authors present their experience of treating anti-cancer drug extravasation by means of a composite surgical technique that consists of infiltration with physiological solution and hyaluronidase and subsequent manual aspiration of solutes alternated with profuse irrigation of the infiltrated area. In the immediate post-op we carry out a medical therapy that consists of calciparine and topic antibiotic and/or steroid creams. Since the year 2000 this technique has been used on 25 patients. We have had neither complications nor scars. Copyright 2005 Wiley-Liss, Inc Surgical treatment of extravasation injuries. Napoli P, Corradino B, Badalamenti G, Tripoli M, Vieni S, Furfaro MF, Cordova A, Moschella F. Source Chirurgia Plastica e Ricostruttiva, Dipartimento di Discipline Chirurgiche ed Oncologiche, Università degli Studi di Palermo, Italy. pietronapoli@libero.it Abstract The authors present their experience of treating anti-cancer drug extravasation by means of a composite surgical technique that consists of infiltration with physiological solution and hyaluronidase and subsequent manual aspiration of solutes alternated with profuse irrigation of the infiltrated area. In the immediate post-op we carry out a medical therapy that consists of calciparine and topic antibiotic and/or steroid creams. Since the year 2000 this technique has been used on 25 patients. We have had neither complications nor scars.

Comparison of Latin American (LA) nuclear cardiology (NC) practice with that in the rest of the world (RoW) will identify areas for improvement and lead to educational activities to reduce radiation exposure from NC. INCAPS collected data on all SPECT and PET procedures performed during a single week in March-April 2013 in 36 laboratories in 10 LA countries (n = 1139), and 272 laboratories in 55 countries in RoW (n = 6772). Eight “best practices” were identified a priori and a radiation-related Quality Index (QI) was devised indicating the number used. Mean radiation effective dose (ED) in LA was higher than in RoW (11.8 vs 9.1 mSv, p