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Background: Systematic reviews can apply the Appraisal of Guidelines for Research & Evaluation (AGREE) II tool to critically appraise clinical practice guidelines (CPGs) for treating low back pain (LBP); however, when appraisals differ in CPG quality rating, stakeholders, clinicians, and policy-makers will find it difficult to discern a unique judgement of CPG quality. We wanted to determine the proportion of overlapping CPGs for LBP in appraisals that applied AGREE II. We also compared inter-rater reliability and variability across appraisals. Methods: For this meta-epidemiological study we searched six databases for appraisals of CPGs for LBP. The general characteristics of the appraisals were collected; the unit of analysis was the CPG evaluated in each appraisal. The inter-rater reliability and the variability of AGREE II domain scores for overall assessment were measured using the intraclass correlation coefficient and descriptive statistics. Results: Overall, 43 CPGs out of 106 (40.6%) overlapped in seventeen appraisals. Half of the appraisals (53%) reported a protocol registration. Reporting of AGREE II assessment was heterogeneous and generally of poor quality: overall assessment 1 (overall CPG quality) was rated in 11 appraisals (64.7%) and overall assessment 2 (recommendation for use) in four (23.5%). Inter-rater reliability was substantial/perfect in 78.3% of overlapping CPGs. The domains with most variability were Domain 6 (mean interquartile range [IQR] 38.6), Domain 5 (mean IQR 28.9), and Domain 2 (mean IQR 27.7). Conclusions: More than one third of CPGs for LBP have been re-appraised in the last six years with CPGs quality confirmed in most assessments. Our findings suggest that before conducting a new appraisal, researchers should check systematic review registers for existing appraisals. Clinicians need to rely on updated CPGs of high quality and confirmed by perfect agreement in multiple appraisals.

Background. International guidelines suggested skin tests with Polyethylene-glycol (PEG) and polysorbate 80 (PS-80), to investigate a possible hypersensitivity to these excipients either to identify subjects at risk of developing allergic reactions to Covid-19 vaccines, or in patients with suspected IgE mediated hypersensitivity reactions (HR) to the Covid-19 vaccine. The main purpose of this study was to investigate the prevalence of PEG and PS sensitization in patients with a clinical history of HR to drugs containing PEG/PS and in patients with a suspected Covid-19 vaccine immediate HR. Methods. This was a multicenter retrospective study conducted by allergists belonging to 20 Italian medical centers. Skin testing was performed in 531 patients with either a clinical history of suspected hypersensitivity reaction (HR) to drugs containing PEG and/or PS-80 (group 1:362 patient) or a suspected HR to Covid-19 vaccines (group 2: 169 patient), as suggested by the AAIITO/SIAAIC guidelines for the "management of patients at risk of allergic reactions to Covid-19 vaccines" [1]. Results. 10/362 (0.02%) had positive skin test to one or both excipients in group 1, 12/169 (7.1%) in group 2 (p less than 0.01). In group 2 HRs to Covid-19 vaccines were immediate in 10/12 of cases and anaphylaxis occurred in 4/12 of patients. Conclusions. The positivity of skin test with PEG and or PS before vaccination is extremely rare and mostly replaceable by an accurate clinical history. Sensitization to PEG and PS has to be investigated in patients with a previous immediate HR to a Covid-19 vaccine, in particular in patients with anaphylaxis.

Objectives: To assess whether the use of the revised Cochrane risk of bias tool for randomized trials (RoB2) in systematic reviews (SRs) adheres to RoB2 guidance. Methods: We searched MEDLINE, Embase, Cochrane Library from 2019 to May 2021 to identify SRs using RoB2. We analyzed methods and results sections to see whether risk of bias was assessed at outcome measure level and applied to primary outcomes of the SR as per RoB2 guidance. The relation between SR characteristics and adequacy of RoB2 use was examined by logistic regression analysis. Results: Two hundred-eight SRs were included. We could assess adherence in 137 SRs as 12 declared using RoB2 but actually used RoB1 and 59 did not report the number of primary outcomes. The tool usage was adherent in 69.3% SRs. Considering SRs with multiple primary outcomes, adherence dropped to 28.8%. We found a positive association between RoB2 guidance adherence and the methodological quality of the reviews assessed by AMSTAR2 (p-for-trend 0.007). Multivariable regression analysis suggested journal impact factor [first quartile vs. other quartiles] was associated with RoB2 adherence (OR 0.34; 95% CI: 0.16-0.72). Conclusions: Many SRs did not adhere to RoB2 guidance as they applied the tool at the study level rather than at the outcome measure level. Lack of adherence was more likely among low and very low quality reviews.

Contains fulltext : 238612.pdf (Publisher’s version ) (Closed access), Nuclear medicine plays an increasingly important role in the management neuroendocrine neoplasms (NEN). Somatostatin analogue (SSA)-based positron emission tomography/computed tomography (PET/CT) and peptide receptor radionuclide therapy (PRRT) have been used in clinical trials and approved by the European Medicines Agency (EMA) and the US Food and Drug Administration (FDA). European Association of Nuclear Medicine (EANM) Focus 3 performed a multidisciplinary Delphi process to deliver a balanced perspective on molecular imaging and radionuclide therapy in well-differentiated neuroendocrine tumours (NETs). NETs form in cells that interact with the nervous system or in glands that produce hormones. These cells, called neuroendocrine cells, can be found throughout the body, but NETs are most often found in the abdomen, especially in the gastrointestinal tract. These tumours may also be found in the lungs, pancreas and adrenal glands. In addition to being rare, NETs are also complex and may be difficult to diagnose. Most NETs are non-functioning; however, a minority present with symptoms related to hypersecretion of bioactive compounds. NETs often do not cause symptoms early in the disease process. When diagnosed, substantial number of patients are already found to have metastatic disease. Several societies' guidelines address Neuroendocrine neoplasms (NENs) management; however, many issues are still debated, due to both the difficulty in acquiring strong clinical evidence in a rare and heterogeneous disease and the different availability of diagnostic and therapeutic options across countries. EANM Focus 3 reached consensus on employing (68)gallium-labelled somatostatin analogue ([(68)Ga]Ga-DOTA-SSA)-based PET/CT with diagnostic CT or magnetic resonance imaging (MRI) for unknown primary NET detection, metastatic NET, NET staging/restaging, suspected extra-adrenal pheochromocytoma/paraganglioma and suspected paraganglioma. Consensus was reached on employing (18)fluorine

Nuclear medicine plays an increasingly important role in the management neuroendocrine neoplasms (NEN). Somatostatin analogue (SSA)-based positron emission tomography/computed tomography (PET/CT) and peptide receptor radionuclide therapy (PRRT) have been used in clinical trials and approved by the European Medicines Agency (EMA) and the US Food and Drug Administration (FDA). European Association of Nuclear Medicine (EANM) Focus 3 performed a multidisciplinary Delphi process to deliver a balanced perspective on molecular imaging and radionuclide therapy in well-differentiated neuroendocrine tumours (NETs). NETs form in cells that interact with the nervous system or in glands that produce hormones. These cells, called neuroendocrine cells, can be found throughout the body, but NETs are most often found in the abdomen, especially in the gastrointestinal tract. These tumours may also be found in the lungs, pancreas and adrenal glands. In addition to being rare, NETs are also complex and may be difficult to diagnose. Most NETs are non-functioning; however, a minority present with symptoms related to hypersecretion of bioactive compounds. NETs often do not cause symptoms early in the disease process. When diagnosed, substantial number of patients are already found to have metastatic disease. Several societies' guidelines address Neuroendocrine neoplasms (NENs) management; however, many issues are still debated, due to both the difficulty in acquiring strong clinical evidence in a rare and heterogeneous disease and the different availability of diagnostic and therapeutic options across countries. EANM Focus 3 reached consensus on employing 68gallium-labelled somatostatin analogue ([68Ga]Ga-DOTA-SSA)-based PET/CT with diagnostic CT or magnetic resonance imaging (MRI) for unknown primary NET detection, metastatic NET, NET staging/restaging, suspected extra-adrenal pheochromocytoma/paraganglioma and suspected paraganglioma. Consensus was reached on employing 18fluorine-fluoro

Background: Heat-and-pepsin-sensitive plant food allergens (PR-10 and profilin) sometimes cause systemic reaction. Objective: To detect the risk factors for systemic reactions induced by labile food allergens. Methods: A retrospective multicenter study was performed on patients with a documented history of systemic allergic reaction to labile plant food allergens and on age-matched controls with a history of oral allergy syndrome (OAS) induced by the same foods. Offending foods, their amount, and state (solid or liquid), and potential cofactors (nonsteroidal anti-inflammatory drugs, protonic pump inhibitors, exercise, alcohol, and fasting) were considered. Results: We studied 89 patients and 81 controls. Sensitization to PR-10 or profilin, IgE to Bet v 1 and/or Bet v 2, and foods causing OAS were similar in the two groups. Twenty patients experienced >1 systemic allergic reaction. Tree nuts, Rosaceae, Apiaceae, and soymilk were the main offending foods. Seventeen (19%) patients were taking a PPI when the systemic reaction occurred (vs 5% in controls; P <.025). The ingestion of the offending food in liquid form (soymilk) was frequent among patients (15%) but unusual among controls (2%; P <.025). Soy milk-induced systemic reactions were independent of PPI treatment. Fasting and excess of allergen, but not NSAID and exercise, were other relevant cofactors for systemic reactions. Systemic reactions occurred without any identifiable cofactor in 39 (44%) cases. Conclusion: PR-10- and profilin-induced systemic reactions are facilitated by PPI, ingestion of large amounts of unprocessed foods, and fasting. Soybean beverages represent a risk for PR-10 hypersensitive patients and should be avoided.

About 75% of colorectal cancers are diagnosed as early stage, in which radical surgery is achievable. In the last decade, in Italy, the overall incidence of colorectal cancer has remained stable, while mortality gradually decreased, which is attributable to early diagnosis and improved medical, surgical and locoregional treatments. The Italian Medical Oncology Association formulated guidelines to manage early-stage colon cancer, including screening, diagnosis, treatment and follow-up, which we herein present.

Background: The standard approach for locally advanced rectal cancer (LARC) is neoadjuvant chemoradiotherapy (nCRT) followed by total mesorectal excision (TME). After nCRT 20% of patients achieve a clinical complete response (pCR) and could be treated with a non-operative management (NOM). Methods: The panel of the Italian Association of Medical Oncology (AIOM) Guidelines on rectal cancer applied the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) approach addressing the following question: Should NOM vs. TME be used for patients with rectal cancer with clinical complete response after nCRT? Five outcomes were identified: disease-free survival (DFS), mortality, local recurrence, colostomy rate, and functional outcomes. Results: Nine studies were included in the analysis. A higher risk of disease recurrence was observed in the NOM group compared to the TME group (RR = 1.69, 95% CI 1.08, 2.64) on the other hand, we observed a slightly positive but not significant effect on mortality of NOM (RR = 0.82, 95% CI 0.46, 1.45). Patients in the NOM group were more likely to experience local recurrence (RR = 5.37, 95% CI 2.56, 11.27) and patients in the TME group were more likely to have a permanent colostomy (RR = 0.15, 95% CI 0.08, 0.29). Only one study evaluated functional outcomes. The overall certainty of evidence was rated as very low. Conclusions: NOM was found to correlate with a higher risk of local recurrence which did not translate in worse OS and a lower colostomy rate. Due to the paucity of evidences, no recommendations are possible. NOM remains an experimental treatment; thus, patients managed with NOM should be enrolled in clinical trials with a dedicated follow-up schedule.

Background: The RAF-MEK-ERK pathway is commonly activated in pancreatic cancer because of a high frequency of KRAS-BRAF mutations. A phase II randomized trial was designed to investigate the activity of sorafenib in combination with chemotherapy in advanced pancreatic cancer. Methods: Locally advanced or metastatic pancreatic adenocarcinoma patients were randomized in a 1:1 ratio to receive cisplatin plus gemcitabine with sorafenib 400. mg bid (arm A) or without sorafenib (arm B). Results: One hundred and fourteen patients were enrolled; of these, 43 (74.6%) patients progressed in arm A and 44 (82.4%) in arm B. Median progression-free survival was 4.3 months (95% CI: 2.7-6.5) and 4.5 months (95% CI: 2.5-5.2), respectively (HR = 0.92; 95% CI: 0.62-1.35). Median overall survival was 7.5 (95% CI: 5.6-9.7) and 8.3 months (95% CI: 6.2-8.7), respectively (HR = 0.95; 95% CI: 0.62-1.48). Response rates were 3.4% in arm A and 3.6% in arm B. Conclusions: Sorafenib does not significantly enhance activity of chemotherapy in advanced pancreatic cancer patients, and therefore should not be assessed in phase III trials

Aims and background. We report a collection of data about early breast cancer in male patients from 13 Italian institutions. Methods and study design. We obtained data from patient charts and performed statistical analysis. The primary end points were overall survival and disease-free survival. Results. A total of 205 men with invasive breast cancer was identified, with a median age of 66 years. Pathological characteristics were heterogeneous for T stage, N stage and HER2 status. Histological subtype was predominantly ductal infiltrating carcinoma. Most of them were hormone receptor positive. Mastectomy was the most common strategy. Postsurgical treatment was not standardized. Patients with large tumors were more likely to be treated with chemotherapy. Disease recurrence was associated with an ER+ and PR+ status. Conclusions. We identified a correlation between relapse and hormone receptor expression, as is the case in female breast cancer.

The general aim of this systematic review is to mitigate breast cancer (BC) overdiagnosis and overtreatment. The specific aim is to summarize available data on the occurrence and features of indolent invasive or in situ (DCIS) BC, and precisely survival of untreated cases, prevalence of occult cancers found in autopsies, frequency of regressive BC. PubMed, Embase and Cochrane Library were systematically searched up to 3/31/2014. Eligibility criteria were: cohort studies, case-control studies, uncontrolled case series assessing survival in women with a diagnosis of BC who did not receive treatment compared to treated women; case series of autopsies estimating the prevalence of undiagnosed BC; cohort studies, case-control studies, uncontrolled case series, case reports assessing the occurrence of spontaneous regression of BC in women with a confirmed histology diagnosis. Untreated BC: 8 cohort studies and 12 case series (3593 BC) were included. In three controlled cohort studies (diagnoses 1978-2006), the 5-years overall survival was 19-43%. Occult BC: 8 case series (2279 autopsies) were included. The prevalence of invasive BC undiagnosed during lifetime range was 0-1.5%, while for DCIS the range was 0.2-14.7%. Spontaneous regression: 2 cohort studies, 3 case reports, 1 case series included. In the cohort studies the relative risk of regression for screen detected compared with nonscreened BC was estimated as 1.2 and 1.1. It seems plausible that around 10% of invasive BC are not symptomatic during life, and that one fith of BC patients if untreated would be alive after 5 years. Around 1 of 10 screen-detected BC may regress according two studies.

This overview describes the principles of the 4th edition of the European Code against Cancer and provides an introduction to the 12 recommendations to reduce cancer risk. Among the 504.6 million inhabitants of the member states of the European Union (EU28), there are annually 2.64 million new cancer cases and 1.28 million deaths from cancer. It is estimated that this cancer burden could be reduced by up to one half if scientific knowledge on causes of cancer could be translated into successful prevention. The Code is a preventive tool aimed to reduce the cancer burden by informing people how to avoid or reduce carcinogenic exposures, adopt behaviours to reduce the cancer risk, or to participate in organised intervention programmes. The Code should also form a base to guide national health policies in cancer prevention. The 12 recommendations are: not smoking or using other tobacco products; avoiding second-hand smoke; being a healthy body weight; encouraging physical activity; having a healthy diet; limiting alcohol consumption, with not drinking alcohol being better for cancer prevention; avoiding too much exposure to ultraviolet radiation; avoiding cancer-causing agents at the workplace; reducing exposure to high levels of radon; encouraging breastfeeding; limiting the use of hormone replacement therapy; participating in organised vaccination programmes against hepatitis B for newborns and human papillomavirus for girls; and participating in organised screening programmes for bowel cancer, breast cancer, and cervical cancer.

PURPOSE: Epithelial ovarian tumors (EOT) are among the most lethal of malignancies in women. We have previously identified ZIC2 as expressed at a higher level in samples of a malignant form (MAL) of EOT than in samples of a form with low malignant potential (LMP). We have now investigated the role of ZIC2 in driving tumor growth and its association with clinical outcomes.EXPERIMENTAL DESIGN: ZIC2 expression levels were analyzed in two independent tumor tissue collections of LMP and MAL. In vitro experiments aimed to test the role of ZIC2 as a transforming gene. Cox models were used to correlate ZIC2 expression with clinical endpoints.RESULTS: ZIC2 expression was about 40-fold in terms of mRNA and about 17-fold in terms of protein in MAL (n = 193) versus LMP (n = 39) tumors. ZIC2 mRNA levels were high in MAL cell lines but undetectable in LMP cell lines. Overexpression of ZIC2 was localized to the nucleus. ZIC2 overexpression increases the growth rate and foci formation of NIH3T3 cells and stimulates anchorage-independent colony formation; downregulation of ZIC2 decreases the growth rate of MAL cell lines. Zinc finger domains 1 and 2 are required for transforming activity. In stage I MAL, ZIC2 expression was significantly associated with overall survival in both univariate (P = 0.046) and multivariate model (P = 0.049).CONCLUSIONS: ZIC2, a transcription factor related to the sonic hedgehog pathway, is a strong discriminant between MAL and LMP tumors: it may be a major determinant of outcome of EOTs. Clin Cancer Res; 18(16); 1-12. ©2012 AACR.

Background. Urticarial vasculitis (UV) is an uncommon type of chronic urticaria (CU), which exhibits leucocytoclastic vasculitis. Painful and long-lasting (> 24 h) weals associated with purpura or bruising are considered indicative of UV. It is often responsive to oral corticosteroids and poorly to oral antihistamines. Hypocomplementaemia and systemic involvement are also commonly reported. Aims. To diagnose patients with UV histologically and then compare their clinical features and response to various treatment regimens. Methods. Biopsies were taken from 312 subjects with CU unresponsive to oral antihistamines; of these, 47 were histologically diagnosed as having UV. Biopsies were taken irrespective of the clinical features of weal eruption. Other diseases known to be associated with small-vessel vasculitis had previously been excluded. Results. Individual weals lasted < 24 h in 57.4% of patients, and pain or tenderness was reported only by 8.6%. Extracutaneous features were present in 81%, hypocomplementaemia in 11% and abnormalities of other laboratory parameters (i.e. raised erythrocyte sedimentation rate, microscopic haematuria) in 76.6%. Hydroxyzine was effective in only one patient. Both oral corticosteroids and cinnarizine were effective in a high percentage of the patients. Conclusion. This diagnostic approach allowed us to identify a large group (47 patients) with UV. Most did not present the clinical (prolonged duration of weals and bruising) and laboratory features that have previously been described as characteristic of UV. Cinnarizine was found to be a valuable treatment option. © 2008 The Author(s).